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1.
Virol J ; 20(1): 81, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37127579

RESUMO

BACKGROUND: Vibrio parahaemolyticus is a major foodborne pathogen that contaminates aquatic products and causes great economic losses to aquaculture. Because of the emergence of multidrug-resistant V. parahaemolyticus strains, bacteriophages are considered promising agents for their biocontrol as an alternative or supplement to antibiotics. In this study, a lytic vibriophage, vB_VpaM_R16F (R16F), infecting V. parahaemolyticus 1.1997T was isolated, characterized and evaluated for its biocontrol potential. METHODS: A vibriophage R16F was isolated from sewage from a seafood market with the double-layer agar method. R16F was studied by transmission electron microscopy, host range, sensitivity of phage particles to chloroform, one-step growth curve and lytic activity. The phage genome was sequenced and in-depth characterized, including phylogenetic and taxonomic analysis. RESULTS: R16F belongs to the myovirus morphotype and infects V. parahaemolyticus, but not nine other Vibrio spp. As characterized by determining its host range, one-step growth curve, and lytic activity, phage R16F was found to highly effective in lysing host cells with a short latent period (< 10 min) and a small burst size (13 plaque-forming units). R16F has a linear double-stranded DNA with genome size 139,011 bp and a G + C content of 35.21%. Phylogenetic and intergenomic nucleotide sequence similarity analysis revealed that R16F is distinct from currently known vibriophages and belongs to a novel genus. Several genes (e.g., encoding ultraviolet damage endonuclease and endolysin) that may enhance environmental competitiveness were found in the genome of R16F, while no antibiotic resistance- or virulence factor-related gene was detected. CONCLUSIONS: In consideration of its biological and genetic properties, this newly discovered phage R16F belongs to a novel genus and may be a potential alternate biocontrol agent.


Assuntos
Bacteriófagos , Vibrio parahaemolyticus , Bacteriófagos/genética , Vibrio parahaemolyticus/genética , Filogenia , Genoma Viral , Especificidade de Hospedeiro
2.
Methods ; 203: 40-45, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35351609

RESUMO

Biological elements, such as genes, exons, coding sequences, are usually expressed as genomic features based on genome-based coordinates. However, the RNA transcription landmarks are usually expressed in the form of RNA-based coordinates. To analyze the association between RNA-related genomic features and RNA transcription landmarks, some tools, such as Guitar, have been developed to convert between these two coordinate systems. However, there remain some issues, such as incomplete transcriptional structures, limitation of transcriptomic view analysis, etc. Therefore, we made corresponding improvements based on Guitar, considered the promoter, 5' cap, and 3' poly-A tail structure in the transcript, standardized the input format of RNA-related genomic features, and finally developed Guitar2. Guitar2 converts genome-based coordinates and RNA-based coordinates with a more accurate strategy. Besides, Guitar2 supports the sketching of three different transcriptional views based on the overall transcripts, messenger RNA, as well as long non-coding RNA. The analysis of m6A modification using Guitar2 shows that m6A modification is significantly enriched near the stop codon in the mRNA, which is consistent with the known results. In conclusion, Guitar2's improvement of coordinate system structure and the provision of full transcriptional view will contribute to the further analysis of RNA-related biological features. Guitar2 is now publicly available from R/Bioconductor: https://bioconductor.org/packages/release/bioc/html/Guitar.html.


Assuntos
RNA Longo não Codificante , Transcriptoma , RNA Mensageiro/genética , Análise de Sequência de RNA/métodos , Software , Transcriptoma/genética
3.
J Obstet Gynaecol Res ; 49(4): 1106-1113, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36759334

RESUMO

This article reviews the findings of clinical studies on gastric-type adenocarcinoma of the cervix to date, outline the molecular biological features identified in recent studies, and discusses the future therapeutic strategies. Gastric-type adenocarcinoma of the cervix is a new classification in the World Health Organization 2014 classification. The World Health Organization 2020 classification further divides cervical tumors into two categories: human papillomavirus-associated and human papillomavirus-independent. Thus, gastric-type adenocarcinoma of the cervix is now classified as a human papillomavirus-independent gastric type. Clinical studies have reported that gastric adenocarcinoma of the cervix is refractory to conventional chemotherapy and radiotherapy, and it is desirable to elucidate its molecular biological mechanism. A series of gene mutations characteristic to the gastric-type adenocarcinoma of the cervix encourage the development of future treatment strategies.


Assuntos
Adenocarcinoma , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Colo do Útero/patologia , Papillomavirus Humano , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Papillomaviridae/genética , Biologia Molecular , Infecções por Papillomavirus/patologia
4.
Semin Cancer Biol ; 77: 194-202, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33607247

RESUMO

In the last decade, a growing attention has been focused on identifying effective therapeutic strategies also in the orphan clinical setting of women with platinum-resistant disease. In this context, secondary cytoreductive surgery (SCS) remains a potential approach only in women with platinum sensitive relapse, but experimental data have been published supporting the role of SCS also in patients with platinum-resistant recurrence. In particular, surgery is emerging as a potential option in specific subgroups of women, such as those patients with low-grade serous histology, or low-volume relapse with disease located in the so-called pharmacological sanctuaries. Furthermore, contrasting evidences have suggested a potential role in this clinical setting of SCS combined with intraperitoneal hyperthermic chemotherapy. In this complex scenario we review here the available evidences regarding the role surgery in ovarian cancer patients with platinum resistant disease, trying also to understand which patients may benefit from this challenging, experimental approach.


Assuntos
Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia/cirurgia , Animais , Antineoplásicos/uso terapêutico , Terapia Combinada/métodos , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica/métodos , Compostos de Platina
5.
BMC Bioinformatics ; 23(1): 411, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36192681

RESUMO

BACKGROUND: Biological age (BA) has been recognized as a more accurate indicator of aging than chronological age (CA). However, the current limitations include: insufficient attention to the incompleteness of medical data for constructing BA; Lack of machine learning-based BA (ML-BA) on the Chinese population; Neglect of the influence of model overfitting degree on the stability of the association results. METHODS AND RESULTS: Based on the medical examination data of the Chinese population (45-90 years), we first evaluated the most suitable missing interpolation method, then constructed 14 ML-BAs based on biomarkers, and finally explored the associations between ML-BAs and health statuses (healthy risk indicators and disease). We found that round-robin linear regression interpolation performed best, while AutoEncoder showed the highest interpolation stability. We further illustrated the potential overfitting problem in ML-BAs, which affected the stability of ML-Bas' associations with health statuses. We then proposed a composite ML-BA based on the Stacking method with a simple meta-model (STK-BA), which overcame the overfitting problem, and associated more strongly with CA (r = 0.66, P < 0.001), healthy risk indicators, disease counts, and six types of disease. CONCLUSION: We provided an improved aging measurement method for middle-aged and elderly groups in China, which can more stably capture aging characteristics other than CA, supporting the emerging application potential of machine learning in aging research.


Assuntos
Envelhecimento , Modelos Biológicos , Idoso , Biomarcadores , Mineração de Dados , Humanos , Aprendizado de Máquina , Pessoa de Meia-Idade
6.
Liver Int ; 42(10): 2283-2298, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35810457

RESUMO

BACKGROUND & AIMS: The multiplicity of hepatocellular carcinoma (HCC) recurrence patterns is the most important determinant of patients' postsurgical survival. A systematic HCC recurrence classification is needed to help prevent and treat postoperative HCC recurrence in the era of precision medicine. METHODS: A total of 1319 patients with recurrent HCC from four hospitals were enrolled and divided into a development cohort (n = 916), internal validation cohort (n = 225) and external validation cohort (n = 178). A comprehensive study of patients' clinicopathological factors and biological features was conducted. RESULTS: Four subtypes of recurrence were identified, which integrated recurrence features, survival, effects on systemic and liver function and potential therapeutics after recurrence: type I (solitary-intrahepatic oligorecurrence); type II (multi-intrahepatic oligorecurrence); type III (progression recurrence) and type IV (hyper-progression recurrence). Type III~IV recurrence indicated exceptionally poor prognosis. Subsequently, two nomogram models were established for type III~IV recurrence prediction, and both demonstrated excellent predictive performance and applicability of pre and postoperative strategy formulation. Multiple biological analyses revealed that HCC cases with type III~IV recurrence were characterized by enrichment in p53 mutations, CCND1 amplification, high proliferation/metastasis potential, inactive metabolism and immune exhaustion features. Over-expression of high mobility group protein 2 (HMGA2) enhanced the highly malignant behaviour of HCC through multiple molecular pathways, making it a potential prognostic predictor and therapeutic target. CONCLUSIONS: This 'recurrent HCC classification' has important potential value in identifying patients with surgical benefit, predicting postsurgical survival and guiding treatment strategies. Multidimensional biological insights also increased knowledge of factors associated with HCC recurrence.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/patologia , Nomogramas , Prognóstico
7.
Respir Res ; 21(1): 224, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854739

RESUMO

Within two decades, there have emerged three highly pathogenic and deadly human coronaviruses, namely SARS-CoV, MERS-CoV and SARS-CoV-2. The economic burden and health threats caused by these coronaviruses are extremely dreadful and getting more serious as the increasing number of global infections and attributed deaths of SARS-CoV-2 and MERS-CoV. Unfortunately, specific medical countermeasures for these hCoVs remain absent. Moreover, the fast spread of misinformation about the ongoing SARS-CoV-2 pandemic uniquely places the virus alongside an annoying infodemic and causes unnecessary worldwide panic. SARS-CoV-2 shares many similarities with SARS-CoV and MERS-CoV, certainly, obvious differences exist as well. Lessons learnt from SARS-CoV and MERS-CoV, timely updated information of SARS-CoV-2 and MERS-CoV, and summarized specific knowledge of these hCoVs are extremely invaluable for effectively and efficiently contain the outbreak of SARS-CoV-2 and MERS-CoV. By gaining a deeper understanding of hCoVs and the illnesses caused by them, we can bridge knowledge gaps, provide cultural weapons for fighting and controling the spread of MERS-CoV and SARS-CoV-2, and prepare effective and robust defense lines against hCoVs that may emerge or reemerge in the future. To this end, the state-of-the-art knowledge and comparing the biological features of these lethal hCoVs and the clinical characteristics of illnesses caused by them are systematically summarized in the review.


Assuntos
Infecções por Coronavirus/epidemiologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/patogenicidade , Betacoronavirus , COVID-19 , Controle de Doenças Transmissíveis , Feminino , Saúde Global , Humanos , Masculino , Prevalência , Medição de Risco , SARS-CoV-2 , Análise de Sobrevida , Organização Mundial da Saúde
8.
J Biol Regul Homeost Agents ; 33(2): 355-364, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30891998

RESUMO

This study aimed to investigate the effect of CD133 on the proliferation and migration of glioma cells and expressions of genes related to cancer stem cells/tumor stem cells (CSC/TSC) as well as their in-vivo oncogenicity. CD133-overexpressing U251-CD133 and U251-mock glioma cells were constructed. The effect of CD133 on in-vitro proliferation and the neurosphere-forming ability of glioma cells was determined by cell count and neurosphere formation assay. Real-Time PCR was performed to detect the expressions of CSC/TSC-related genes in the CD133-transfected cells. Nude mouse subcutaneous tumor formation assay was used to determine the effect of CD133 on the in-vivo oncogenicity of glioma cells. In serum-containing medium, human CD133 had no impact on the proliferation of U251 glioma cells, but the neural stem cells placed in serum-free medium promoted neurosphere formation. In the presence of CD133, the expressions of CSC/TSC-related genes were upregulated to varying degrees in glioma cells; CD133 greatly enhanced the in-vivo oncogenicity. In conclusion, CD133 promoted the upregulation of CSC/TSC-related genes in glioma cells, while enhancing the neurosphere-forming ability and in-vivo oncogenicity.


Assuntos
Antígeno AC133/metabolismo , Neoplasias Encefálicas/patologia , Glioma/patologia , Células-Tronco Neoplásicas/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Camundongos , Camundongos Nus , Regulação para Cima
9.
Appl Microbiol Biotechnol ; 103(19): 7819-7833, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31463545

RESUMO

Acidithiobacillus thiooxidans (A. thiooxidans) is a widespread, mesophilic, obligately aerobic, extremely acidophilic, rod-shaped, and chemolithoautotrophic gram-negative gammaproteobacterium. It can obtain energy and electrons from the oxidation of reducible sulfur, and it can fix carbon dioxide and assimilate nitrate, nitrite, and ammonium to satisfy carbon and nitrogen requirement. This bacterium exists as different genomovars and its genome size range from 3.02 to 3.97 Mb. Here, we highlight the recent advances in the understanding of the general biological features of A. thiooxidans, as well as the genetic diversity and the sulfur oxidation pathway system. Additionally, the potential applications of A. thiooxidans were summarized including the recycling of metals from metal-bearing ores, electric wastes, and sludge, the improvement of alkali-salinity soils, and the removal of sulfur from sulfur-containing solids and gases.


Assuntos
Acidithiobacillus thiooxidans/metabolismo , Biotecnologia/métodos , Enxofre/metabolismo , Acidithiobacillus thiooxidans/classificação , Acidithiobacillus thiooxidans/genética , Oxirredução
10.
Arch Gynecol Obstet ; 298(5): 873-879, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30255344

RESUMO

PURPOSE: To identify women affected by recurrent ovarian cancer who benefit from secondary cytoreductive surgery (SCS), analyse their clinical and biological features and investigate the role of minimally invasive surgery (MIS) and hyperthermic intraperitoneal-based chemotherapy (HIPEC) in this subset of patients. METHODS: This narrative review examines the data available from the updated literature. An electronic literature search was conducted in PubMed Medline databases for articles published from 1990 to 2018. RESULTS: Retrospective studies and preliminary data from the AGO-Desktop III trial show that cytoreductive surgery is associated with improved post-relapse survival in patients with platinum-sensitive relapse, compared to chemotherapy alone. This benefit is more evident in patients treated with complete or optimal primary debulking surgery at referral centres, who did not receive bevacizumab in first-line chemotherapy, and who present a localized pattern of disease. MIS has been proven to be a favourable approach to achieve a complete secondary debulking, reducing peri- and postoperative comorbidities. The application of HIPEC to SCS is associated with an improvement in oncological outcomes by preliminary results. CONCLUSIONS: While waiting for the final results of the ongoing randomized controlled trials, SCS seems feasible and safe in selected patients with recurrent ovarian cancer. Recently, more attention has been focused on the biological features of ovarian tumours, such as BRCA status. Further studies and molecular research should be conducted to identify individualized and targeted therapies in the treatment of ovarian cancer recurrences.


Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias Ovarianas/cirurgia , Feminino , Humanos , Recidiva Local de Neoplasia , Neoplasias Ovarianas/patologia , Estudos Retrospectivos
11.
Arch Virol ; 162(9): 2829-2834, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28550433

RESUMO

The Rhabdoviridae is a diverse family of negative-sense single-stranded RNA viruses which infects mammals, birds, reptiles, fish, insects and plants. Herein, we reported the isolation and characterization of 6 novel viruses from diseased fish collected from China including SCRV-QY, SCRV-SS, SCRV-GM, CmRV-FS, MsRV-SS, OmbRV-JM. The typical clinical symptom of diseased fish was hemorrhaging. Efficient propagation of these isolates in a Chinese perch brain cell line was determined by means of observation of cytopathic effect, RT-PCR and electron microscopy. Sequence alignment and phylogenetic analysis of the complete G protein sequences revealed that these isolates were clustered into one monophyletic lineage belonging to the species Siniperca chuatsi rhabdovirus.


Assuntos
Doenças dos Peixes/virologia , Variação Genética , Rhabdoviridae/genética , Rhabdoviridae/patogenicidade , Animais , China/epidemiologia , Doenças dos Peixes/epidemiologia , Doenças dos Peixes/patologia , Peixes
12.
Artigo em Russo | MEDLINE | ID: mdl-37796070

RESUMO

OBJECTIVE: To study the outcomes of depression at a late age during a 3-year prospective follow-up in patients with various immunophenotypes. MATERIAL AND METHODS: A cohort of patients with depressive disorders who were treated in a gerontopsychiatric hospital and re-examined after 1 and 3 years. The group with immunophenotype A (with increased activity of leukocyte elastase (LE) and complex depressions, comorbid with anxiety and senesto-hypochondriac disorders) included 20 people: 6 men (30%) and 14 women (70%), median age was 68 years. A depressive episode (DE) was diagnosed in 13 patients (65%) with recurrent depressive disorder (RDD) and in 7 patients (35%) with bipolar affective disorder (BAD). The group with immunophenotype B (with reduced activity of LE and prolonged apathetic-adynamic depression) included 31 people: 10 men (32.3%) and 21 women (67.7%), the median age was 68 years. DE was diagnosed in 20 patients (64.5%) with RDD, 9 patients (29%) with BAD, and in 2 patients (6.5%) with a single DE. The patients were examined using clinical, psychometric, immunological and clinical- follow-up methods (after 1 and 3 years). RESULTS: More favorable course of the disease with the formation of high-quality remission was observed in patients with immunophenotype A (95% of cases after 1 and 3 years; χ2=10.44; p=0.001 and χ2=11.97; p=0.001, respectively). In patients with immunophenotype B, an unfavorable course of the disease prevailed (83.9 and 87.1% of cases after 1 and 3 years) with the formation of low-quality remissions (with residual depressive disorders, the development of repeated depressive phases and chronification of depression). CONCLUSION: The study revealed the relationship between clinical and biological features and the course of late-life depression.


Assuntos
Transtorno Bipolar , Depressão , Masculino , Humanos , Feminino , Idoso , Depressão/diagnóstico , Depressão/epidemiologia , Estudos Prospectivos , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Prognóstico , Comorbidade , Elastase de Leucócito
13.
Crit Rev Oncol Hematol ; 190: 104120, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37660930

RESUMO

In recent years, the incidence of cancers is continuously increasing in young adults. Early-onset cancer (EOC) is usually defined as patients with cancers under the age of 50, and may represent a unique subgroup due to its special disease features. Overall, EOCs often initiate at a young age, present as a better physical performance but high degree of malignancy. EOCs also share common epidemiological and hereditary risk factors. In this review, we discuss several representative EOCs which were well studied previously. By revealing their clinical and molecular similarities and differences, we consider the group of EOCs as a unique subtype compared to ordinary cancers. In consideration of EOC as a rising threat to human health, more researches on molecular mechanisms, and large-scale, prospective clinical trials should be carried out to further translate into improved outcomes.


Assuntos
Neoplasias , Adulto Jovem , Humanos , Estudos Prospectivos , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapia , Fatores de Risco
14.
Biotechnol Genet Eng Rev ; : 1-12, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37212030

RESUMO

To explore the significance of the analysis of pathological characteristics of breast cancer and the detection of myeloid-derived suppressor cell (MDSC) levels in peripheral blood for the evaluation of biological characteristics. 138 breast cancer patients were enrolled as the research group, while 138 patients with benign breast diseases were included as the control group. All patients underwent pathological analysis and detection of peripheral blood MDSCs levels, progesterone receptor (PR), estrogen receptor (ER), human epidermal growth factor receptor 2 (HER-2), and proliferating cell nuclear antigen (Ki-67). A factorial study of stage I, II, and III breast cancer patients showed significant differences in clinicopathological characteristics, including age, tumor size, lymph node metastases, histological grading, Neuropsychiatric Inventory (NPI) score, pathological type, and family history (P < 0.05). The research group had higher levels of peripheral blood MDSCs and different cell surface markers compared to the control group (P<0.05). Positive expression of biological molecules in breast cancer, such as PR, ER, HER-2, and Ki-67, had significant differences based on lymph node metastasis and tumor size (P < 0.05). The quality of survival scores was higher in stages I and II compared to stage III (P < 0.05). Age, recurrence, metastasis, and other pathological characteristics of breast cancer have a direct impact on clinical outcomes and survival rates. Peripheral blood levels of MDSCs and other cell surface markers are significantly elevated, serving as a crucial benchmark for the subsequent evaluation of breast cancer progression.

15.
Exp Oncol ; 45(2): 139-150, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37824778

RESUMO

The statistical data of the recent decades demonstrate a rapid growth of breast cancer (BCa) incidence and a tendency toward its increase especially in young women. In the structure of morbidity of women in the age group of 18-29 years, BCa ranks first and in the age range of 15-39 years, BCa is one of the leading causes of mortality. According to the data of the epidemiological and clinical studies, the young age is an independent unfavorable prognostic factor of BCa that is associated with an unfavorable prognosis and low survival rates and is considered an important predictor of the disease aggressiveness, a high risk of metastasis and recurrence. The variability of clinicopathological and molecular-biological features of BCa in patients of different age groups as well as the varying course of the disease and different responses to the therapy are mediated by many factors. The analysis of the literature data on the factors and mechanisms of BCa initiation in patients of different age groups demonstrates that the pathogen- esis of BCa depends not only on the molecular-genetic alterations but also on the metabolic disorders caused by the current social and household rhythm of life and nutrition peculiarities. All these factors affect both the general con- dition of the body and the formation of an aggressive microenvironment of the tumor lesion. The identified features of transcriptome and the differential gene expression give evidence of different regulations of the immune response and the metabolic processes in BCa patients of different age groups. Association between the high expression of the components of the stromal microenvironment and the inflammatory immune infiltrate as well as the increased vascu- larization of the tumor lesion has been found in BCa tissue of young patients. Proving the nature of the formation of the landscape comprising molecular-genetic, cytokine, and immune factors of the tumor microenvironment will undoubtedly contribute to our understanding of the mechanisms of tumor growth allowing for the development of algorithms for delineating the groups at high risk of tumor progression, which requires more careful monitoring and personalized treatment approach. Th s will be helpful in the development of innovative technologies for complex BCa treatment.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Medicina de Precisão , Prognóstico , Citocinas , Microambiente Tumoral/genética
16.
Steroids ; 199: 109287, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37517592

RESUMO

Reports on structural modification of heterosteroids through various reactions, and developed synthetic routes have considerably increased over the last decade. The present review encompasses the applicable approaches dealing with the utility of reactive moieties in various steroids for the synthesis of fused bicyclic pyridines, and binary bicyclic pyridines all over the years. The different sections include the synthesis of steroids-fused, and binary quinolines, pyridopyrimidines, imidazopyridines, spirocyclic imidazopyridines, pyrazolopyridines, thienopyridines, pyridinyl-thiazoles, and tetrazolopyridine hybrids, as well as, the diverse biological applications of these heterocyclic steroids. The researchers' interest was principally focused on investigating the flexibility of synthetic strategies for various derivatives of natural steroids and building proposals based on heterocyclic steroids for drug discovery, biological assessments, and synthetic applications.

17.
Psychiatry Res ; 324: 115226, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37116323

RESUMO

Co-occurrence of antipsychotic-induced weight gain (AIWG) and therapeutic response (TR) did exist in clinic but was rarely studied. This study aims to identify potential TR/ AIWG biotypes and explore the clinical, genetic and neuroimaging features. This study enrolled 3030 patients to identify potential TR/AIWG biotypes and explore the clinical, genetic and neuroimaging features. We found three biotypes: TR+nonAIWG (46.91%), TR+AIWG (18.82%), and nonTR+nonAIWG (34.27%). TR+AIWG showed lower weight and lipid level at baseline, but higher changing rate, and higher genetic risk of obesity than TR+nonAIWG and nonTR+nonAIWG. GWAS identified ADIPOQ gene related to TR+AIWG biotypes and top-ranked loci enriched in one-carbon metabolic process, which related to both schizophrenia and metabolic dysfunction. Genetically predicted TR+AIWG was associated with higher odds of diabetes (OR=1.05). The left supplementary motor area was significantly negatively correlated with PRS of obesity. The distinguishing ability with multi-omics data to identify TR+AIWG reached 0.787. In a word, the "thin" patients with a higher risk of obesity are the target population of early intervention.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Antipsicóticos/efeitos adversos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Aumento de Peso/genética , Obesidade/induzido quimicamente , Obesidade/genética , Fatores de Risco
18.
In Vivo ; 36(2): 859-864, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35241543

RESUMO

BACKGROUND/AIM: There are few models predicting breast cancer prognosis among patients receiving neoadjuvant chemotherapy (NAC) for estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative (luminal) breast cancer. We examined whether biological features (BFs) of residual tumors are prognostic factors following NAC. PATIENTS AND METHODS: We enrolled patients with remnant tumors following NAC for luminal breast cancer and evaluated clinical stage, pathological stage, BFs prior to NAC, and BFs following NAC as prognostic factors. BFs were divided into high and low risk using the previously reported YR-IHC4 model calculated according to ER, progesterone receptor (PgR), HER2, and the proliferation marker Ki-67. RESULTS: A total of 57 patients were enrolled in the current study. We observed a statistically significant difference in relapse-free survival (RFS) between the BF risk categories via YR-IHC4 predictions following NAC (p=0.044). The 5-year RFS rates of the BF low- and high-risk groups following NAC were 84.2% and 52.5%, respectively. CONCLUSION: BFs of residual tumors following NAC may be important prognostic factors in luminal breast cancer.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
19.
Acta Clin Belg ; 77(2): 261-267, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32935644

RESUMO

BACKGROUND: The aim of this study was to identify early clinical and laboratory predictive factors of a severe coronavirus disease 2019 (COVID-19). METHODS: A retrospective study was conducted on adult patients hospitalized for COVID-19 in our hospital. Diagnosis was based on a positive real-time reverse transcription-polymerase chain reaction (RT-PCR) on nasopharyngeal samples. The cohort was divided into two groups, i.e. a favorable evolution (FE) group and an unfavorable evolution (UFE) group, including intensive care unit (ICU) and deceased patients.Results: A total of 198 patients were enrolled in the study, with 138 FE (70%) and 60 UFE (30%). Older age, male gender, comorbidities and dyspnea at admission constituted significantly worse prognosis factors. Among laboratory features, lymphocyte and platelet counts as well as corrected glomerular filtration rate were significantly lower in UFE patients, while neutrophil to lymphocyte ratio, inflammation biomarkers, creatinine, aspartate aminotransferase, lactate dehydrogenase (LDH), glycemia and D-dimer were significantly higher. Procalcitonin and LDH appeared as the most accurate variables according to receiver operating characteristic curves. CONCLUSIONS: This Belgian study revealed clinical and laboratory features able to predict high risk of ICU requirement, or even death, at admission time. These results provide a potential tool for patient's triage in a context of pandemic.Abbreviations: COVID-19: coronavirus disease 2019; ARDS: acute respiratory distress syndrome; DIC: disseminated intravascular coagulopathy; MOF: multi-organ failure; RT-PCR: real-time reverse transcription-polymerase chain reaction; UFE: unfavorable evolution; ICU: intensive care unit; EDTA: ethylenediamine tetraacetic acid; WBC: white blood cell count; Hb: hemoglobin level; PCT: procalcitonin; Na: sodium; K: potassium; PT: total protein, CRP: c-reactive protein; Cr: creatinine; ALAT: alanine aminotransferase; ALAT: aspartate aminotransferase; TB: total bilirubin, LDH: lactate dehydrogenase, FERR: ferritin; hs-Tnt: high sensitive-troponin T; cGFR: corrected glomerular filtration rate; QR: quick ratio; DDIM: D-dimer; FIB: fibrinogen; SD: standard deviation; IQR: interquartile ranges; ROC: receiver operating characteristics; ECMO: extracorporeal membrane oxygenation; NLR: neutrophil to lymphocyte ratio; AUC: area under the curve; BMI: body mass index.


Assuntos
COVID-19 , COVID-19/diagnóstico , Humanos , Laboratórios , Masculino , Pandemias , Estudos Retrospectivos , SARS-CoV-2
20.
Zh Nevrol Psikhiatr Im S S Korsakova ; 122(6. Vyp. 2): 36-42, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35797194

RESUMO

OBJECTIVE: To analyze clinical parameters and effectiveness of therapy in depressed patients of late age with different activity of enzymes of energy, glutamate metabolism and antioxidant glutathione system in platelets and red blood cells. MATERIAL AND METHODS: The study included 53 hospitalized patients (41 women and 12 men), aged 60 to 86 years (median - 66 years), with a depressive episode of mild to marked severity within the framework of recurrent depressive disorder, bipolar affective disorder or a single depressive episode according to ICD-10. The patients were examined using clinical, psychometric, biochemical and statistical methods. Psychometric assessment of patients' condition was performed before the start of therapy and on the 28th day of treatment using HAMD-17 and HARS. Blood sampling was carried out to determine the activity of cytochrome c-oxidase (COX), glutathione reductase (GR), glutathione S-transferase (GST) and glutamate dehydrogenase (GDH). RESULTS: Cluster analysis revealed 3 clusters (Cl.1, Cl.2, Cl.3), which differed in biochemical indicators. In Cl.1 (n=24, 45.2%), there was a decrease in the activity of COX (p<0.05) and a decrease of GR activity in red blood cells and GST activity in platelets (p<0.001). Patients of Cl.2 (n=11, 20.8%) had increased COX activity (p<0.001) and decreased GDH activity (p<0.001). In patients of Cl.3 (n=18, 34%) the enzyme activity was similar to that in the controls. Later age at disease onset was observed in Cl.1 compared to Cl.2 (51 years [40; 60.5] and 32 years [19; 59], p=0.052). Compared with Cl.2 and Cl.3, patients of Cl.1 significantly more often (p<0.05) had apathetic depressions (41.7%), while complex depressions were observed almost 2 times less often than in Cl.2 (50% and 91.9%, p<0.05). The effectiveness and tolerability of psychopharmacotherapy was higher in Cl.3. CONCLUSION: There is a relationship between the nature of changes in metabolic parameters and differences in the phenomenology and course of late-age depression. The results of the study open up new directions in the field of predicting the effectiveness of therapy and the development of personalized therapeutic approaches to improve the effectiveness and safety of treatment of depressed elderly patients.


Assuntos
Transtorno Bipolar , Depressão , Idoso , Antioxidantes , Depressão/tratamento farmacológico , Feminino , Glutationa , Glutationa Redutase/metabolismo , Glutationa Transferase , Humanos , Masculino
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