RESUMEN
PURPOSE: Glioma-associated oncogene homolog-1 (GLI1) is amplified in human glioblastoma, and there is growing evidence suggesting its significant role in tumor development and metastasis. Our aim was to investigate the role of the GLI-1 gene in the progression of colorectal cancer (CRC) and its correlation with various clinicopathological features. Additionally, we examined the impact of the GLI-1 gene and other factors on the prognosis of CRC. METHODS: We analyzed a total of 98 confirmed CRC cases and adjacent normal tissue controls. Patients suspected of having colon cancer underwent a colonoscopy and targeted biopsy, while those with rectal cancer underwent CT scans and MRI. GLI1 expression was detected using real-time PCR assay, Western blotting, and immunohistochemistry. RESULTS: The GLI1 gene was observed to be overexpressed in tumor tissues at both the protein and mRNA levels (p < 0.05). In addition, GLI1 overexpression was significantly associated with various factors such as tumor invasion (T3/T4), presence of lymph nodes, lymph node metastasis (LNM), stage (III/IV), tumor site (colon), tumor size (≥ 3 cm), localization (nucleocytoplasmic), strong staining intensity and recurrence (p < 0.05). The results of survival analysis showed that the patients with overexpression of GLI1 had a significantly lower DFS rate which was 21 months compared to those with normal expression who had 31 months (p < 0.05). Moreover, individuals with early onset disease (15 months) were more likely to have cytoplasmic localization of the GLI1 gene as opposed to nucleo-cytoplasmic localization of GLI1 which presented late-onset disease( 23 months) (p < 0.05). Finally, Stage and PNI (p < 0.05) were found to independently affect outcomes of CRC according to Cox regression analysis. CONCLUSION: High expression of GLI-1 in CRC is associated with adverse pathology and poor prognosis for patients. The correlation between cytoplasmic localization of GLI-1 and reduced disease-free survival holds potential for guiding prognosis and treatment. Further research is needed to develop strategies targeting GLI-1 for improved outcomes.
Asunto(s)
Biomarcadores de Tumor , Neoplasias Colorrectales , Proteína con Dedos de Zinc GLI1 , Humanos , Proteína con Dedos de Zinc GLI1/metabolismo , Proteína con Dedos de Zinc GLI1/genética , Masculino , Femenino , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Persona de Mediana Edad , Pronóstico , Anciano , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Supervivencia sin Enfermedad , Adulto , Regulación Neoplásica de la Expresión Génica , Metástasis LinfáticaRESUMEN
This study aims at reporting the indigenous knowledge of the medicinal flora from the inhabitants of surroundings of the World's largest artificial planted forest "Changa Manga", Pakistan. Data were collected by direct interviews and group meetings from 81 inhabitants including 32 local healers having information regarding the use of indigenous medicinal plants over a period of one year. Different statistical tools were applied to analyze the data including Frequency citation (FC), Relative frequency citation (RFC), Use Value, Factor of informants consensus and fidelity level. This study reported 73 plant species belonging to 37 plant families and 46 genera. The majority of plant species belong to compositae family. The most commonly used medicinal plants were P. hysterophorus L., P. dactylifera L., S. indicum L, P. harmala L., P. emblica L., and A. indica A.Juss. The greatest number of species was used to cure gastrointestinal disorders. The highest fidelity level (68.18%) was of E. helioscopia to cure gastrointestinal disorders. Maximum fresh uses (17) were reported by C. dactylon (L.) Pars. While the highest number of species reporting fresh uses in similar number was 13. In this study, five novel plants are being reported for the first time in Pakistan for their ethnomedicinal worth. Our data reflect unique usage of the medicinal plants in the study area. The statistical tools used in the study proved useful in pointing the most important and disease category specific plants. High use value plant and the new reported medicinal plants might prove an important source of the isolation of pharmacologically active compounds.
Este estudo tem como objetivo relatar o conhecimento indígena sobre a flora medicinal dos habitantes do entorno da maior floresta artificial plantada do mundo, a Changa Manga, no Paquistão. Os dados foram coletados por meio de entrevistas diretas e reuniões em grupo de 81 habitantes, incluindo 32 curandeiros locais, com informações sobre o uso de plantas medicinais indígenas durante o período de um ano. Diferentes ferramentas estatísticas foram aplicadas para analisar os dados, incluindo citação de frequência (FC), citação de frequência relativa (RFC), valor de uso, fator de consenso dos informantes e nível de fidelidade. Este estudo relatou 73 espécies de plantas pertencentes a 37 famílias de plantas e 46 gêneros. A maioria das espécies de plantas pertence à família Compositae. As plantas medicinais mais utilizadas foram P. hysterophorus L., P. dactylifera L., S. indicum L., P. harmala L., P. emblica L. e A. indica A. Juss. O maior número de espécies foi usado para curar distúrbios gastrointestinais. O maior nível de fidelidade (68,18%) foi de E. helioscopia para cura de distúrbios gastrointestinais. Os usos máximos em fresco (17) foram relatados por C. dactylon (L.) Pars. enquanto o maior número de espécies relatando usos frescos em número semelhante foi de 13. Neste estudo, cinco novas plantas estão sendo relatadas pela primeira vez no Paquistão por seu valor etnomedicinal. Nossos dados refletem o uso exclusivo das plantas medicinais na área de estudo. As ferramentas estatísticas utilizadas no estudo mostraram-se úteis para apontar as plantas mais importantes e específicas da categoria de doença. Plantas de alto valor de uso e as novas plantas medicinais relatadas podem ser uma importante fonte de isolamento de compostos farmacologicamente ativos.
Asunto(s)
Humanos , Plantas Medicinales , Bosques , Enfermedades Gastrointestinales , Pueblos Indígenas , Medicina Tradicional , PakistánRESUMEN
Termites are known as social insects worldwide. Presently in China 473 species, 44 genera and 4 families of termites have been reported. Of them, 111 Reticulitermes species are widely spread in different zones of China. The dispersion flight season of these Chinese Reticulitermes species are usually started from February to June, but in some regions different species are distributed, sharing their boundaries and having overlapping flight seasons. These reasons become important sources of hybridization between two different heterospecific populations of termites. It was confirmed that the fertilized eggs and unfertilized eggs of some Reticulitermes termites have the capacity of cleavage. While the unfertilized eggs of R. aculabialis, R. chinensis and R. labralis cleaved normally and the only R. aculabialis unfertilized eggs develop in embryos. While, the R. flaviceps and R. chinensis were observed with their abnormal embryonic development, and not hatching of eggs parthenogenetically. They were reported more threatening to Chinese resources as they propagate with parthenogenesis, hybridization and sexual reproduction. Eggshell and macrophiles of eggs play important roles in species identification and control. Although, they are severe pests and cause a wide range of damages to wooden structures and products in homes, buildings, building materials, trees, crops, and forests in China's Mainland.
Os cupins são conhecidos como insetos sociais em todo o mundo. Atualmente na China foram relatadas 473 espécies, 44 gêneros e 4 famílias de cupins. Destas, 111 espécies de Reticulitermes estão amplamente distribuídas em diferentes zonas da China. A temporada de voo de dispersão dessas espécies chinesas de Reticulitermes geralmente começa de fevereiro a junho, mas em algumas regiões diferentes espécies são distribuídas, compartilhando seus limites e tendo temporadas de voo sobrepostas. Essas razões tornam-se importantes fontes de hibridização entre duas populações heteroespecíficas de cupins. Foi confirmado que os ovos fertilizados e não fertilizados de alguns cupins Reticulitermes possuem capacidade de clivagem. Já os ovos não fertilizados de R. aculabialis, R. chinensis e R. labralis clivaram normalmente, e os únicos ovos não fertilizados de R. aculabialis se desenvolvem em embriões. R. flaviceps e R. chinensis foram observados com desenvolvimento embrionário anormal, e não eclosão de ovos por partenogênese. Eles foram relatados como mais ameaçadores para os recursos chineses à medida que se propagam com partenogênese, hibridização e reprodução sexual. Casca de ovo e macrófilos de ovos desempenham papéis importantes na identificação e controle de espécies, embora sejam pragas graves e causem uma ampla gama de danos a estruturas e produtos de madeira em residências, edifícios, materiais de construção, árvores, plantações e florestas na China continental.
Asunto(s)
Animales , Partenogénesis , Reproducción , Isópteros/crecimiento & desarrollo , China , Hibridación GenéticaRESUMEN
Germin-like proteins (GLPs) play an important role against various stresses. Vitis vinifera L. genome contains 7 GLPs; many of them are functionally unexplored. However, the computational analysis may provide important new insight into their function. Currently, physicochemical properties, subcellular localization, domain architectures, 3D structures, N-glycosylation & phosphorylation sites, and phylogeney of the VvGLPs were investigated using the latest computational tools. Their functions were predicted using the Search tool for the retrieval of interacting genes/proteins (STRING) and Blast2Go servers. Most of the VvGLPs were extracellular (43%) in nature but also showed periplasmic (29%), plasma membrane (14%), and mitochondrial- or chloroplast-specific (14%) expression. The functional analysis predicted unique enzymatic activities for these proteins including terpene synthase, isoprenoid synthase, lipoxygenase, phosphate permease, receptor kinase, and hydrolases generally mediated by Mn+ cation. VvGLPs showed similarity in the overall structure, shape, and position of the cupin domain. Functionally, VvGLPs control and regulate the production of secondary metabolites to cope with various stresses. Phylogenetically VvGLP1, -3, -4, -5, and VvGLP7 showed greater similarity due to duplication while VvGLP2 and VvGLP6 revealed a distant relationship. Promoter analysis revealed the presence of diverse cis-regulatory elements among which CAAT box, MYB, MYC, unnamed-4 were common to all of them. The analysis will help to utilize VvGLPs and their promoters in future food programs by developing resistant cultivars against various biotic (Erysiphe necator and in Powdery Mildew etc.) and abiotic (Salt, drought, heat, dehydration, etc.) stresses.
As proteínas do tipo germin (GLPs) desempenham um papel importante contra vários estresses. O genoma de Vitis vinifera L. contém 7 GLPs; muitos deles são funcionalmente inexplorados. No entanto, a análise computacional pode fornecer informações importantes sobre sua função. Atualmente, as propriedades físico-químicas, localização subcelular, arquitetura de domínio, estruturas 3D, sítios de N-glicosilação e fosforilação e estudos filogenéticos dos VvGLPs foram conduzidos usando as ferramentas computacionais mais recentes. Suas funções foram previstas usando a ferramenta Search para recuperação de genes/proteínas em interação (STRING) e servidores Blast2Go. A maioria dos VvGLPs são extracelulares (43%) na natureza, mas também mostraram expressão periplasmática (29%), na membrana plasmática (14%) e específica para mitocôndrias ou cloroplastos (14%). A análise funcional previu atividades enzimáticas únicas para essas proteínas, incluindo terpeno sintase, isoprenoide sintase, lipoxigenase, fosfato permease, receptor quinase e hidrolases geralmente mediadas por cátion Mn +. VvGLPs mostraram similaridade na estrutura geral, forma e posição do domínio cupin. Funcionalmente, os VvGLPs controlam e regulam a produção de metabólitos secundários para lidar com vários estresses. Filogeneticamente, VvGLP1, -3, -4, -5 e VvGLP7 mostraram maior similaridade devido à duplicação, enquanto VvGLP2 e VvGLP6 revelaram uma relação distante. A análise do promotor revelou a presença de diversos elementos cis-reguladores, entre os quais CAAT box, MYB, MYC, sem nome-4, sendo comum a todos eles. A análise ajudará a utilizar VvGLPs e seus promotores em programas alimentares futuros, desenvolvendo cultivares resistentes contra vários estresses bióticos (Erysiphe necator e no oídio, etc.) e abióticos (sal, seca, calor, estresse hídrico, etc.).
Asunto(s)
Estrés Fisiológico/genética , Proteínas , Vitis/genéticaRESUMEN
Abstract Ferns are often used by indigenous people in Khyber Pakhtunkhwa, Pakistan. This study was designed to collect the ethnomedicinal and traditional knowledge of these locals about this group of vascular plants. Forty taxa belong to nineteen genera and ten families are used in the treatment of different diseases. The Pteridaceae was the most representative family with twelve taxa (30%), followed by Athyriaceae and Dryopteridaceae with six taxa each (30%), and Thelypteridaceae with five taxa (12.5%). Regarding the genera, Adiantum, Asplenium and Dryopteris ranked first with four taxa each (30%), followed by Aleuritopteris, Diplazium, Pteris and Equisetum with three taxa each (30%), followed by Athyrium, Oeosporangium, Polystichum and Pseudophegopteris with two taxa each (20%). These taxa were commonly used in the treatment of respiratory disorders i.e. asthma, bronchitis, emphysema, pneumonia; intestinal ulcer, stomach, urinary ailments and skin disorders by the methods of decoction and infusion. Traditional knowledge about ethnomedicinal plants is a valuable and essential source for the discovery of allopathic, herbal and homeopathic medicines.
Resumo As samambaias são frequentemente usadas pelos indígenas em Khyber Pakhtunkhwa, Paquistão. Este estudo foi desenhado para coletar o conhecimento etnomedicinal e tradicional desses moradores sobre este grupo de plantas vasculares. Quarenta táxons pertencem a dezenove gêneros, e dez famílias são utilizadas no tratamento de diferentes doenças. Pteridaceae foi a família mais representativa com doze táxons (30%), seguida por Athyriaceae e Dryopteridaceae com seis táxons cada (30%), e Thelypteridaceae com cinco táxons (12,5%). Em relação aos gêneros, Adiantum, Asplenium e Dryopteris ficaram em primeiro lugar com quatro táxons cada (30%), seguidos por Aleuritopteris, Diplazium, Pteris e Equisetum com três táxons cada (30%), e Athyrium, Oeosporangium, Polystichum e Pseudophegopteris com dois táxons cada (20%). Estes táxons foram comumente usados no tratamento de distúrbios respiratórios, isto é, asma, bronquite, enfisema, pneumonia; úlcera intestinal, estômago, doenças urinárias e doenças da pele pelos métodos de decocção e infusão. O conhecimento tradicional sobre plantas etnomedicinais é uma fonte valiosa e essencial para a descoberta de medicamentos alopáticos, fitoterápicos e homeopáticos.
Asunto(s)
Humanos , Plantas Medicinales , Helechos , Tracheophyta , Pakistán , Fitoterapia , Medicina TradicionalRESUMEN
Abstract Ferns are often used by indigenous people in Khyber Pakhtunkhwa, Pakistan. This study was designed to collect the ethnomedicinal and traditional knowledge of these locals about this group of vascular plants. Forty taxa belong to nineteen genera and ten families are used in the treatment of different diseases. The Pteridaceae was the most representative family with twelve taxa (30%), followed by Athyriaceae and Dryopteridaceae with six taxa each (30%), and Thelypteridaceae with five taxa (12.5%). Regarding the genera, Adiantum, Asplenium and Dryopteris ranked first with four taxa each (30%), followed by Aleuritopteris, Diplazium, Pteris and Equisetum with three taxa each (30%), followed by Athyrium, Oeosporangium, Polystichum and Pseudophegopteris with two taxa each (20%). These taxa were commonly used in the treatment of respiratory disorders i.e. asthma, bronchitis, emphysema, pneumonia; intestinal ulcer, stomach, urinary ailments and skin disorders by the methods of decoction and infusion. Traditional knowledge about ethnomedicinal plants is a valuable and essential source for the discovery of allopathic, herbal and homeopathic medicines.
Resumo As samambaias são frequentemente usadas pelos indígenas em Khyber Pakhtunkhwa, Paquistão. Este estudo foi desenhado para coletar o conhecimento etnomedicinal e tradicional desses moradores sobre este grupo de plantas vasculares. Quarenta táxons pertencem a dezenove gêneros, e dez famílias são utilizadas no tratamento de diferentes doenças. Pteridaceae foi a família mais representativa com doze táxons (30%), seguida por Athyriaceae e Dryopteridaceae com seis táxons cada (30%), e Thelypteridaceae com cinco táxons (12,5%). Em relação aos gêneros, Adiantum, Asplenium e Dryopteris ficaram em primeiro lugar com quatro táxons cada (30%), seguidos por Aleuritopteris, Diplazium, Pteris e Equisetum com três táxons cada (30%), e Athyrium, Oeosporangium, Polystichum e Pseudophegopteris com dois táxons cada (20%). Estes táxons foram comumente usados no tratamento de distúrbios respiratórios, isto é, asma, bronquite, enfisema, pneumonia; úlcera intestinal, estômago, doenças urinárias e doenças da pele pelos métodos de decocção e infusão. O conhecimento tradicional sobre plantas etnomedicinais é uma fonte valiosa e essencial para a descoberta de medicamentos alopáticos, fitoterápicos e homeopáticos.
RESUMEN
Abstract Germin-like proteins (GLPs) play an important role against various stresses. Vitis vinifera L. genome contains 7 GLPs; many of them are functionally unexplored. However, the computational analysis may provide important new insight into their function. Currently, physicochemical properties, subcellular localization, domain architectures, 3D structures, N-glycosylation & phosphorylation sites, and phylogeney of the VvGLPs were investigated using the latest computational tools. Their functions were predicted using the Search tool for the retrieval of interacting genes/proteins (STRING) and Blast2Go servers. Most of the VvGLPs were extracellular (43%) in nature but also showed periplasmic (29%), plasma membrane (14%), and mitochondrial- or chloroplast-specific (14%) expression. The functional analysis predicted unique enzymatic activities for these proteins including terpene synthase, isoprenoid synthase, lipoxygenase, phosphate permease, receptor kinase, and hydrolases generally mediated by Mn+ cation. VvGLPs showed similarity in the overall structure, shape, and position of the cupin domain. Functionally, VvGLPs control and regulate the production of secondary metabolites to cope with various stresses. Phylogenetically VvGLP1, -3, -4, -5, and VvGLP7 showed greater similarity due to duplication while VvGLP2 and VvGLP6 revealed a distant relationship. Promoter analysis revealed the presence of diverse cis-regulatory elements among which CAAT box, MYB, MYC, unnamed-4 were common to all of them. The analysis will help to utilize VvGLPs and their promoters in future food programs by developing resistant cultivars against various biotic (Erysiphe necator and in Powdery Mildew etc.) and abiotic (Salt, drought, heat, dehydration, etc.) stresses.
Resumo As proteínas do tipo germin (GLPs) desempenham um papel importante contra vários estresses. O genoma de Vitis vinifera L. contém 7 GLPs; muitos deles são funcionalmente inexplorados. No entanto, a análise computacional pode fornecer informações importantes sobre sua função. Atualmente, as propriedades físico-químicas, localização subcelular, arquitetura de domínio, estruturas 3D, sítios de N-glicosilação e fosforilação e estudos filogenéticos dos VvGLPs foram conduzidos usando as ferramentas computacionais mais recentes. Suas funções foram previstas usando a ferramenta Search para recuperação de genes/proteínas em interação (STRING) e servidores Blast2Go. A maioria dos VvGLPs são extracelulares (43%) na natureza, mas também mostraram expressão periplasmática (29%), na membrana plasmática (14%) e específica para mitocôndrias ou cloroplastos (14%). A análise funcional previu atividades enzimáticas únicas para essas proteínas, incluindo terpeno sintase, isoprenoide sintase, lipoxigenase, fosfato permease, receptor quinase e hidrolases geralmente mediadas por cátion Mn +. VvGLPs mostraram similaridade na estrutura geral, forma e posição do domínio cupin. Funcionalmente, os VvGLPs controlam e regulam a produção de metabólitos secundários para lidar com vários estresses. Filogeneticamente, VvGLP1, -3, -4, -5 e VvGLP7 mostraram maior similaridade devido à duplicação, enquanto VvGLP2 e VvGLP6 revelaram uma relação distante. A análise do promotor revelou a presença de diversos elementos cis-reguladores, entre os quais CAAT box, MYB, MYC, sem nome-4, sendo comum a todos eles. A análise ajudará a utilizar VvGLPs e seus promotores em programas alimentares futuros, desenvolvendo cultivares resistentes contra vários estresses bióticos (Erysiphe necator e no oídio, etc.) e abióticos (sal, seca, calor, estresse hídrico, etc.).
RESUMEN
Antibiotics are used for postsurgical wound healing purposes but unfortunately, resistance against them demands some alternatives for quick recovery. Sepsis of wounds is a challenge for medical as well as veterinary professionals. Nanoparticles have significant advantages in wound treatment and drug resistance reversal. This study was conducted to appreciate emerging alternates of antibiotics like zinc oxide nanoparticles and plant extracts in topical application. Zinc oxide is considered a good wound healer and its nanoparticles are easy to access. So, the efficacies of zinc oxide nanoparticles and sweet flag plant extract ointments were tested to compare modern and traditional therapeutics as sweet flag is considered a pure medicinal plant. Rabbits were selected for this study due to the healing properties of their skin. Wounds were inflicted on the thoracolumbar region and treated for 29 days post-surgically daily with normal saline and the ointment of zinc oxide nanoparticles and sweet flag extract ointment, prepared in a hydrophilic solvent. Wound shrinkage was observed daily and histopathological analysis was made and results were compared. Zinc oxide nanoparticles ointment showed the most satisfactory results for every parameter included in the study. No side effects of its topical application were observed. Healing was normal without any complications. The preparations of zinc oxide nanoparticles may help in the era of antibiotic resistance as topical drugs in the future.
Asunto(s)
Acorus , Nanopartículas , Herida Quirúrgica , Óxido de Zinc , Animales , Conejos , Óxido de Zinc/farmacología , Herida Quirúrgica/veterinaria , Pomadas , Antibacterianos/farmacología , Extractos Vegetales/farmacologíaRESUMEN
T cells are critical in destroying cancer cells by recognizing antigens presented by MHC molecules on cancer cells or antigen-presenting cells. Identifying and targeting cancer-specific or overexpressed self-antigens is essential for redirecting T cells against tumors, leading to tumor regression. This is achieved through the identification of mutated or overexpressed self-proteins in cancer cells, which guide the recognition of cancer cells by T-cell receptors. There are two main approaches to T cell-based immunotherapy: HLA-restricted and HLA-non-restricted Immunotherapy. Significant progress has been made in T cell-based immunotherapy over the past decade, using naturally occurring or genetically engineered T cells to target cancer antigens in hematological malignancies and solid tumors. However, limited specificity, longevity, and toxicity have limited success rates. This review provides an overview of T cells as a therapeutic tool for cancer, highlighting the advantages and future strategies for developing effective T cell cancer immunotherapy. The challenges associated with identifying T cells and their corresponding antigens, such as their low frequency, are also discussed. The review further examines the current state of T cell-based immunotherapy and potential future strategies, such as the use of combination therapy and the optimization of T cell properties, to overcome current limitations and improve clinical outcomes.
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BACKGROUND: Suppressor of fused (SuFu) is a tumor-suppressor gene that regulates hedgehog signaling. Its involvement in some malignancies is broadly accepted. However, its association with colorectal cancer (CRC) pathogenesis is not clear. Likewise, no study has clearly associated blood-based inflammatory biomarkers with cancer diagnosis/prognosis as yet. AIM: Our goal was to look at SuFu expression levels in CRC patients and its relationship with other clinicopathological factors. Additionally, we looked into the function of a few blood-based biomarkers in CRC and whether or not a combined strategy at the genetic and clinical levels can be applied in CRC. METHODS: The investigation included 98 histopathologically confirmed CRC samples and adjacent normal tissues (controls). A colonoscopy was followed by a targeted biopsy for each suspected colon cancer patient. A CT scan and MRI were also performed on every patient with rectal cancer. Real-time polymerase chain reaction and immunohistochemistry (IHC) were used for assessment. A Beckman Coulter DxH900 was used to examine blood parameters. A Beckman Coulter DxI800 was used to identify pretreatment carcinoma embryonic antigens (CEA) and carbohydrate antigens (CA 19-9) in CRC patients. RESULTS: The expression of SuFu was associated with gender, education, passive smoking, tumor grade, perineural invasion (PNI), lymph node metastasis (LNM), node status, stage, vital status, and recurrence (p < 0.05). In the combined analysis, the areas under the curve produced by the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and red cell distribution width (RDW) were the greatest (AUCRDW+PLR+NLR = 0.91, 95% CI: 0.86-0.93, p < 0.05). Furthermore, the most severe pathological features were linked to RDW, PLR, NLR, and HPR. SuFu expression, node status, LNM, PNI, and stage all had significant correlations with OS and DFS rates in IHC-based univariate survival analysis (p < 0.05). According to the Cox regression, CA-19.9 had a strong independent predictive link with 3-year DFS (p < 0.05). CONCLUSION: In CRC, SuFu was downregulated both transcriptionally and translationally, was primarily nucleo-cytoplasmic, and was expressed less in high-grade tumors. In addition, SuFu was linked to a poor overall and disease-free survival rate. It may be possible to use SuFu as a therapeutic target for CRC in the future. However, SuFu expression had no effect on RDW, PLR, NLR, or HPR serum levels.
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Forkhead Box M1 (FOXM1)-a key cell cycle regulator is a member of the Forkhead transcription factor family. It plays a key role in embryogenesis and cell proliferation and has been strongly linked to various solid tumors. We sought to understand the regulation of FOXM1 in colorectal cancer (CRC), as well as if and to what extent other clinicopathological characteristics are associated with FOXM1. The investigation comprised 98 CRC samples and normal tissues (controls). All colon cancer patients had a colonoscopy and targeted biopsy. All rectal cancer patients had a CT and MRI. Real-time PCR, Immunohistochemistry, and Western blotting were used to evaluate FOXM1 expression, and the findings were analyzed using SPSS (v.26). FOXM1 mRNA and protein expression were substantially upregulated in tumor tissues, with the majority of these proteins localized in nucleo-cytoplasm. Elevated protein levels of FOXM1 were strongly correlated with lower education level, larger tumor size, lymph node status, lymphovascular invasion (LVI), perineural invasion (PNI), lymph node metastasis (LNM), tumor invasion depth (subserosal and serosal invasion), late stage (III and IV), localization (nucleo-cytoplasmic), intensity (strong) and recurrence. Based on survival analysis, FOXM1 overexpression and nucleo-cytoplasmic localization were associated with shorter disease-free survival while stage and PNI were linked to poorer overall and disease-free survival. According to the results of the Cox regression analysis, stage and PNI were significant predictors of prognosis in CRC patients. FOXM1 expression was elevated in CRC and was linked to reduced disease-free survival. These findings support prior reports and hence FOXM1 can be an important prognostic marker for CRC and a promising therapeutic target. Additionally, we found a link between poor disease-free survival and FOXM1's nucleo-cytoplasmic localization. However, since the sample size of this study was small, further research is needed to validate our findings.
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Neoplasias Colorrectales , Proteína Forkhead Box M1 , Humanos , Proteína Forkhead Box M1/genética , Factores de Transcripción Forkhead/genética , Pronóstico , Metástasis Linfática , Neoplasias Colorrectales/patología , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Línea Celular TumoralRESUMEN
Abstract Traditional medicine is cheaper and easily available to local people, to care for most frequent diseases in the Northern parts of Pakistan. Our study aimed at inventorying medicine from local plants, documenting their uses, and assessing their market value in 2015-2018 during spring, summer, and winter seasons. A total of 15 trips were made, 5 in each season. Semi-structured interviews with 165 inhabitant's age range between 20-80 years were conducted, analyzed the data is analyzed using Relative frequency of citation(RFC), Use Value(UV), Fidelity Level(FL), Informants consensus factor(ICF), and Jaccard index(JI) to find the most frequent and well-known used species in the area. A total of 86 species belonging to 39 vascular plant families, 33 genera were documented as medicinally important. Family Asteraceae was observed as the dominant family among all the families with 10 species, the leaf was the most used parts and decoction 36% was the most preferred preparation type. Herb was the predominant life form (67%). The maximum UV (0.92) was demonstrated by J. adhatoda L. species, while A. sativum L. shows maximum RFC (0.58), the highest ICF value represented by diarrhea and dermatitis 0.92, and high FL value is recorded 100%. According to our collections, wild species were 45%, invasive species were 38% and cultivated 17% recorded, dicots species were recorded more 81%. Seven 7 medicinal species is being economically important and export to the local and international market of the world, whereas P. integrima L. species were the most exported species according to the local dealers. The investigated area is rural and the local people depend on the area's plants for their health needs, and other uses like a vegetable, fuelwood, fodder, etc. The current result of RFC, UV, ICF, FL, and JI shows that medicinal flora needs to be pharmacologically and phytochemically investigated to prove their efficacy. The documentation of medicinal knowledge is important to preserve this precious old knowledge before it is lost forever, due to technological and environmental changes in the world.
Resumo A medicina tradicional é mais barata e facilmente disponível à população local para cuidar das doenças mais frequentes nas áreas do norte do Paquistão. Nosso estudo teve como objetivo inventariar medicamentos de plantas locais, documentar seus usos e avaliar seu valor de mercado em 2015-2018 durante as temporadas de primavera, verão e inverno. Foram feitas 15 viagens, 5 em cada temporada. Foram realizadas entrevistas semiestruturadas com 165 moradores na faixa etária de 20 a 80 anos, com dados analisados por meio de frequência relativa de citação (RFC), valor de uso (UV), nível de fidelidade (FL), fator de consenso de informantes (CIF), e o índice de Jaccard (JI) para encontrar as espécies utilizadas mais frequentes e conhecidas na área. Um total de 86 espécies pertencentes a 39 famílias de plantas vasculares, 33 gêneros foram documentados como medicamente importantes. A família Asteraceae foi observada como a família dominante entre todas as famílias com 10 espécies, a folha foi a parte mais utilizada e a decocção 36% foi o tipo de preparação mais preferido. A erva foi a forma de vida predominante (67%). O UV máximo (0,92) foi demonstrado pelas espécies de J. adhatoda L., enquanto A. sativum L. mostra RFC máximo (0,58), o maior valor de ICF representado por diarreia e dermatite 0,92, e alto valor de FL é registrado 100%. De acordo com nossas coleções, as espécies selvagens foram 45%, as espécies invasoras 38% e as cultivadas 17% registradas, as espécies dicotiledôneas foram registradas mais 81%. Sete espécies medicinais estão sendo economicamente importantes e exportadas para o mercado local e internacional do mundo, enquanto as espécies de P. integrima L. foram as espécies mais exportadas de acordo com os comerciantes locais. A área investigada é rural e a população local depende das plantas da área para suas necessidades de saúde e outros usos como vegetal, lenha, forragem etc. O resultado atual de RFC, UV, ICF, FL e JI mostra que a flora medicinal precisa ser investigada farmacológica e fitoquimicamente para comprovar sua eficácia. A documentação do conhecimento medicinal é importante para preservar esse precioso conhecimento antigo antes que se perca para sempre, devido às mudanças tecnológicas e ambientais do mundo.
Asunto(s)
Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Plantas Medicinales , Pakistán , Encuestas y Cuestionarios , Hojas de la Planta , Etnobotánica , Fitoterapia , Medicina TradicionalRESUMEN
Increased endothelial cell (EC) permeability is a cardinal feature of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Tyrosine phosphorylation of VE-cadherin is a key determinant of EC barrier disruption. However, the identity and role of tyrosine kinases in this context are incompletely understood. Here we report that Spleen Tyrosine Kinase (Syk) is a key mediator of EC barrier disruption and lung vascular leak in sepsis. Inhibition of Syk by pharmacological or genetic approaches, each reduced thrombin-induced EC permeability. Mechanistically, Syk associates with and phosphorylates VE-cadherin to cause EC permeability. To study the causal role of endothelial Syk in sepsis-induced ALI, we used a remarkably efficient and cost-effective approach based on gene transfer to generate EC-ablated Syk mice. These mice were protected against sepsis-induced loss of VE-cadherin and inflammatory lung injury. Notably, the administration of Syk inhibitor R788 (fostamatinib); currently in phase II clinical trial for the treatment of COVID-19, mitigated lung injury and mortality in mice with sepsis. These data identify Syk as a novel kinase for VE-cadherin and a druggable target against ALI in sepsis.
Asunto(s)
Lesión Pulmonar Aguda , Antígenos CD , Cadherinas , Síndrome de Dificultad Respiratoria , Sepsis , Quinasa Syk , Animales , Ratones , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Antígenos CD/metabolismo , Cadherinas/metabolismo , Permeabilidad Capilar , Pulmón/metabolismo , Sepsis/complicaciones , Quinasa Syk/metabolismo , FosforilaciónRESUMEN
Traditional medicine is cheaper and easily available to local people, to care for most frequent diseases in the Northern parts of Pakistan. Our study aimed at inventorying medicine from local plants, documenting their uses, and assessing their market value in 2015-2018 during spring, summer, and winter seasons. A total of 15 trips were made, 5 in each season. Semi-structured interviews with 165 inhabitant's age range between 20-80 years were conducted, analyzed the data is analyzed using Relative frequency of citation(RFC), Use Value(UV), Fidelity Level(FL), Informants consensus factor(ICF), and Jaccard index(JI) to find the most frequent and well-known used species in the area. A total of 86 species belonging to 39 vascular plant families, 33 genera were documented as medicinally important. Family Asteraceae was observed as the dominant family among all the families with 10 species, the leaf was the most used parts and decoction 36% was the most preferred preparation type. Herb was the predominant life form (67%). The maximum UV (0.92) was demonstrated by J. adhatoda L. species, while A. sativum L. shows maximum RFC (0.58), the highest ICF value represented by diarrhea and dermatitis 0.92, and high FL value is recorded 100%. According to our collections, wild species were 45%, invasive species were 38% and cultivated 17% recorded, dicots species were recorded more 81%. Seven 7 medicinal species is being economically important and export to the local and international market of the world, whereas P. integrima L. species were the most exported species according to the local dealers. The investigated area is rural and the local people depend on the area's plants for their health needs, and other uses like a vegetable, fuelwood, fodder, etc. The current result of [...].
A medicina tradicional é mais barata e facilmente disponível à população local para cuidar das doenças mais frequentes nas áreas do norte do Paquistão. Nosso estudo teve como objetivo inventariar medicamentos de plantas locais, documentar seus usos e avaliar seu valor de mercado em 2015-2018 durante as temporadas de primavera, verão e inverno. Foram feitas 15 viagens, 5 em cada temporada. Foram realizadas entrevistas semiestruturadas com 165 moradores na faixa etária de 20 a 80 anos, com dados analisados por meio de frequência relativa de citação (RFC), valor de uso (UV), nível de fidelidade (FL), fator de consenso de informantes (CIF), e o índice de Jaccard (JI) para encontrar as espécies utilizadas mais frequentes e conhecidas na área. Um total de 86 espécies pertencentes a 39 famílias de plantas vasculares, 33 gêneros foram documentados como medicamente importantes. A família Asteraceae foi observada como a família dominante entre todas as famílias com 10 espécies, a folha foi a parte mais utilizada e a decocção 36% foi o tipo de preparação mais preferido. A erva foi a forma de vida predominante (67%). O UV máximo (0,92) foi demonstrado pelas espécies de J. adhatoda L., enquanto A. sativum L. mostra RFC máximo (0,58), o maior valor de ICF representado por diarreia e dermatite 0,92, e alto valor de FL é registrado 100%. De acordo com nossas coleções, as espécies selvagens foram 45%, as espécies invasoras 38% e as cultivadas 17% registradas, as espécies dicotiledôneas foram registradas mais 81%. Sete espécies medicinais estão sendo economicamente importantes e exportadas para o mercado local e internacional do mundo, enquanto as espécies de P. integrima L. foram as espécies mais exportadas de acordo com os comerciantes locais. A área investigada é rural e a população local depende das [...].
Asunto(s)
Etnobotánica/economía , Etnobotánica/tendencias , Plantas Medicinales/clasificaciónRESUMEN
Abstract Traditional medicine is cheaper and easily available to local people, to care for most frequent diseases in the Northern parts of Pakistan. Our study aimed at inventorying medicine from local plants, documenting their uses, and assessing their market value in 2015-2018 during spring, summer, and winter seasons. A total of 15 trips were made, 5 in each season. Semi-structured interviews with 165 inhabitants age range between 20-80 years were conducted, analyzed the data is analyzed using Relative frequency of citation(RFC), Use Value(UV), Fidelity Level(FL), Informants consensus factor(ICF), and Jaccard index(JI) to find the most frequent and well-known used species in the area. A total of 86 species belonging to 39 vascular plant families, 33 genera were documented as medicinally important. Family Asteraceae was observed as the dominant family among all the families with 10 species, the leaf was the most used parts and decoction 36% was the most preferred preparation type. Herb was the predominant life form (67%). The maximum UV (0.92) was demonstrated by J. adhatoda L. species, while A. sativum L. shows maximum RFC (0.58), the highest ICF value represented by diarrhea and dermatitis 0.92, and high FL value is recorded 100%. According to our collections, wild species were 45%, invasive species were 38% and cultivated 17% recorded, dicots species were recorded more 81%. Seven 7 medicinal species is being economically important and export to the local and international market of the world, whereas P. integrima L. species were the most exported species according to the local dealers. The investigated area is rural and the local people depend on the area's plants for their health needs, and other uses like a vegetable, fuelwood, fodder, etc. The current result of RFC, UV, ICF, FL, and JI shows that medicinal flora needs to be pharmacologically and phytochemically investigated to prove their efficacy. The documentation of medicinal knowledge is important to preserve this precious old knowledge before it is lost forever, due to technological and environmental changes in the world.
Resumo A medicina tradicional é mais barata e facilmente disponível à população local para cuidar das doenças mais frequentes nas áreas do norte do Paquistão. Nosso estudo teve como objetivo inventariar medicamentos de plantas locais, documentar seus usos e avaliar seu valor de mercado em 2015-2018 durante as temporadas de primavera, verão e inverno. Foram feitas 15 viagens, 5 em cada temporada. Foram realizadas entrevistas semiestruturadas com 165 moradores na faixa etária de 20 a 80 anos, com dados analisados por meio de frequência relativa de citação (RFC), valor de uso (UV), nível de fidelidade (FL), fator de consenso de informantes (CIF), e o índice de Jaccard (JI) para encontrar as espécies utilizadas mais frequentes e conhecidas na área. Um total de 86 espécies pertencentes a 39 famílias de plantas vasculares, 33 gêneros foram documentados como medicamente importantes. A família Asteraceae foi observada como a família dominante entre todas as famílias com 10 espécies, a folha foi a parte mais utilizada e a decocção 36% foi o tipo de preparação mais preferido. A erva foi a forma de vida predominante (67%). O UV máximo (0,92) foi demonstrado pelas espécies de J. adhatoda L., enquanto A. sativum L. mostra RFC máximo (0,58), o maior valor de ICF representado por diarreia e dermatite 0,92, e alto valor de FL é registrado 100%. De acordo com nossas coleções, as espécies selvagens foram 45%, as espécies invasoras 38% e as cultivadas 17% registradas, as espécies dicotiledôneas foram registradas mais 81%. Sete espécies medicinais estão sendo economicamente importantes e exportadas para o mercado local e internacional do mundo, enquanto as espécies de P. integrima L. foram as espécies mais exportadas de acordo com os comerciantes locais. A área investigada é rural e a população local depende das plantas da área para suas necessidades de saúde e outros usos como vegetal, lenha, forragem etc. O resultado atual de RFC, UV, ICF, FL e JI mostra que a flora medicinal precisa ser investigada farmacológica e fitoquimicamente para comprovar sua eficácia. A documentação do conhecimento medicinal é importante para preservar esse precioso conhecimento antigo antes que se perca para sempre, devido às mudanças tecnológicas e ambientais do mundo.
RESUMEN
Background: Neoadjuvant chemoradiotherapy (NACRT) is an established treatment option for locally advanced rectal cancer (LARC). Patients achieving pathological complete response (pCR) following NACRT have better oncological outcomes and may be subjected to wait and watch policy as well. The aim of this study was to identify predictors of pCR in LARC following NACRT. Materials and Methods: A retrospective analysis of a prospectively maintained colorectal cancer database from January 2018 to December 2019 was undertaken. A total of 129 patients of LARC who were subjected to conventional long course NACRT, followed by surgery were included in the study. Pathological response to NACRT was assessed using Mandard grading system and response was categorized as pCR or not-pCR. Correlation between various clinico pathological parameters and pCR was determined using univariate and multivariate logistic regression analysis. Results: Mean age of patients was 53.79 ± 1.303 years. Complete pathological response (Mandard Gr 1) was achieved in 24/129 (18.6%) patients. Age of patients more than 60 years (P = 0.011; odds ratio [OR] 3.194, 95% confidence interval [CI] 1.274-8.011), interval between last dose of NACRT and surgery >8 weeks (P = 0.004; OR 4.833, 95% CI 1.874-12.467), well-differentiated tumors (P < 0.0001; OR 32.00, 95% CI 10.14-100.97) and node-negative disease (P = 0.003; OR 111.0, 95% CI 2.51-48.03) proved to be strong predictors of pCR. Conclusion: Older age, longer interval between NACRT and surgery, node-negative disease and favorable tumor grade help in achieving better pCR rates. Awareness of these variables can be valuable in counseling patients regarding prognosis and treatment options.
Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Estadificación de Neoplasias , Resultado del Tratamiento , Neoplasias del Recto/patología , QuimioradioterapiaRESUMEN
Background: Anal fistula is often considered to be a dilemma because of the need to maintain a fine balance between postoperative incontinence and recurrence. We tried to find whether apprehension of causing incontinence should stop us from performing fistulectomy. The aim of this study was to determine whether fistulectomy was associated with increased rate of fecal incontinence and recurrence, compared to other procedures used for the treatment of anal fistula. Methods: It was a prospective, single center, observational study. All patients with anal fistula operated at a tertiary care teaching institute over a period of two years were included in the study. Recurrence rates and fecal incontinence were compared between patients subjected to fistulectomy and other procedures for treatment of fistula in ano. Results: A total of 124 patients with anal fistula were included. 92.8% patients were ≤ 60 years of age with high male preponderance (89.5%). Perineal discharge was the commonest complaint (95.96%). Intersphincteric (47.58%) followed by transphincteric fistulas (45.16%) accounted for the majority of fistulas. Fistulectomy was the most common procedure, performed in 90 (72.58%) patients. Incontinence occurred in 8/90 (8.88%) from the fistulectomy group and 2/34 (5.9%) patients in other surgery group, p=0.726. Recurrence occurred in 8/90 (8.88%) from the fistulectomy group and 8/34 (23.5%) patients from other surgery group, p=0.038. Overall rates of incontinence and recurrence were 8.1% and 12.9% respectively. Conclusion: Fistulectomy, as compared to other procedures, results in less chances of recurrence without compromising continence.
RESUMEN
Juglans regia L. are nutritious fruit bearing plants mostly found in Northern areas of Pakistan. The population of walnuts was explored from district Dir and Swat Khyber Pakhtunkhwa, Pakistan for their geographical, climatic and chemical divergence. The geographical differences such as altitude, latitude and longitude whereas climatic differences viz. soil EC, soil pH, precipitations, intensity of light, temperature and soil temperature. In both districts TPC ranged from 211.2±0.6 to 227.8±0.4 mg/100g, RSA ranged from 43.32±1.5% to 52.18±0.4%, conductivity ranged from 296.43±0.6 to 312.22±0.3 S/m and elemental composition such as iron, copper, calcium, zinc and magnesium in Dir differs from 0.312±0.032, 0.209±0.13, 20.0±0.313, 0.406±0.10 and 10.2±0.030 mg/L to 0.543±0.65, 0.698±0.82, 28.7±0.234, 0.685±0.15 and 17.6±0.015 mg/L respectively. Altitude and temperature showed a correlation with total phenolics contents and radical scavenging activity while soil pH, precipitations, soil temperature, soil Ec and light intensity indicated a weak correlation with chemical traits of walnuts. Further studies of walnuts are needed to explore their therapeutically important phytochemicals to succeed naturally pharmaceutical nutrients of the maximum significance for the health of human beings.
Asunto(s)
Juglans , Altitud , Humanos , Nueces , Pakistán/epidemiología , SueloRESUMEN
This study aims at reporting the indigenous knowledge of the medicinal flora from the inhabitants of surroundings of the World's largest artificial planted forest "Changa Manga", Pakistan. Data were collected by direct interviews and group meetings from 81 inhabitants including 32 local healers having information regarding the use of indigenous medicinal plants over a period of one year. Different statistical tools were applied to analyze the data including Frequency citation (FC), Relative frequency citation (RFC), Use Value, Factor of informants consensus and fidelity level. This study reported 73 plant species belonging to 37 plant families and 46 genera. The majority of plant species belong to compositae family. The most commonly used medicinal plants were P. hysterophorus L., P. dactylifera L., S. indicum L, P. harmala L., P. emblica L., and A. indica A.Juss. The greatest number of species was used to cure gastrointestinal disorders. The highest fidelity level (68.18%) was of E. helioscopia to cure gastrointestinal disorders. Maximum fresh uses (17) were reported by C. dactylon (L.) Pars. While the highest number of species reporting fresh uses in similar number was 13. In this study, five novel plants are being reported for the first time in Pakistan for their ethnomedicinal worth. Our data reflect unique usage of the medicinal plants in the study area. The statistical tools used in the study proved useful in pointing the most important and disease category specific plants. High use value plant and the new reported medicinal plants might prove an important source of the isolation of pharmacologically active compounds.