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1.
Trop Biomed ; 41(1): 84-96, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38852138

RESUMO

Rhipicephalus microplus, known as the hard tick, is a vector for the parasites Babesia spp. and Anaplasma marginale, both of which can cause significant financial losses to the livestock industry. There is currently no effective vaccine for R. microplus tick infestations, despite the identification of numerous prospective tick vaccine candidates. As a result, the current research set out to develop an immunoinformatics-based strategy using existing methods for designing a multi-epitope based vaccination that is not only effective but also safe and capable of eliciting cellular and humoral immune responses. First, R. microplus proteins Bm86, Subolesin, and Bm95 were used to anticipate and link B and T-cell epitopes (HTL and CTL) to one another. Antigenicity testing, allergenicity assessment, and toxicity screening were just a few of the many immunoinformatics techniques used to identify potent epitopes. Multi-epitope vaccine design was chosen based on the antigenic score 0.935 that is promising vaccine candidate. Molecular docking was used to determine the nature of the interaction between TLR2 and the vaccine construct. Finally, molecular dynamic simulation was used to assess the stability and compactness of the resulting vaccination based on docking scores. The developed vaccine was shown to be stable, have immunogenic qualities, be soluble, and to have high expression by in silico cloning. These findings suggest that experimental investigation of the multi-epitope based vaccine designed in the current study will produce achievable vaccine candidates against R. microplus ticks, enabling more effective control of infestations.


Assuntos
Proteínas de Artrópodes , Biologia Computacional , Epitopos de Linfócito B , Epitopos de Linfócito T , Rhipicephalus , Vacinas , Rhipicephalus/imunologia , Animais , Vacinas/imunologia , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/genética , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito B/imunologia , Simulação de Acoplamento Molecular , Infestações por Carrapato/prevenção & controle , Infestações por Carrapato/veterinária , Infestações por Carrapato/imunologia , Simulação de Dinâmica Molecular , Epitopos/imunologia , Imunoinformática , Antígenos , Glicoproteínas de Membrana , Proteínas Recombinantes
2.
Front Vet Sci ; 11: 1373842, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38860006

RESUMO

Introduction: Blood parasites pose a significant threat to livestock production in southern Egypt, yet there is a scarcity of information regarding their circulation and epidemiology in sheep in this region. This study aimed to investigate the seroprevalence of blood parasite infections in sheep in Assiut governorate, Upper Egypt. Methods: A total of 400 blood samples were collected from sheep of varying ages and genders. The preliminary screening for the presence of piroplasms, mainly Babesia and Theileria spp., via microscopic examination, followed by investigation of the potential risk factors linked with the exposure to infection. Moreover, molecular identification of both parasites on some of positive samples was performed using PCR targeting Babesia 18S rRNA and Theileria annulata Tams1 gene. Results: The microscopic examination revealed that among the examined sheep, there was an overall prevalence of blood parasites at 44% (176 out of 400), with Babesia spp. observed in 14% (56 out of 400) and Theileria spp. in 30% (120 out of 400). Furthermore, the infection rate was non-significantly higher in young animals (50%) compared to adults (38.5%) (P = 0.246). Male sheep exhibited a significantly higher vulnerability to both parasites' infection (63.3%) compared to females (35.7%) (P = 0.011). Interestingly, the prevalence of both blood parasites was significantly higher during the cold season (66.1%) compared to the hot season (15.9%) (P = < 0.001). The molecular analysis identified the presence of Babesia ovis and Theileria annulata among a subsample of the positive sheep's bloods films. The identified species were recorded in the GenBank™ databases and assigned specific accession numbers (OQ360720 and OQ360719 for B. ovis), and (OP991838 for T. annulata). Conclusions: Taken together, this study confirms a high prevalence of piroplasmosis and offers epidemiological and molecular insights into blood parasites in sheep from Upper Egypt, highlighting the importance of detecting these parasites in various hosts and their competent vectors (ticks).

3.
RSC Adv ; 14(21): 14702, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38716110

RESUMO

Expression of Concern for 'Palladium supported on mixed-metal-organic framework (Co-Mn-MOF-74) for efficient catalytic oxidation of CO' by Reda S. Salama et al., RSC Adv., 2021, 11, 4318-4326, https://doi.org/10.1039/D0RA09970H.

4.
Protein Sci ; 33(6): e5019, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38747396

RESUMO

AF9 (MLLT3) and its paralog ENL(MLLT1) are members of the YEATS family of proteins with important role in transcriptional and epigenetic regulatory complexes. These proteins are two common MLL fusion partners in MLL-rearranged leukemias. The oncofusion proteins MLL-AF9/ENL recruit multiple binding partners, including the histone methyltransferase DOT1L, leading to aberrant transcriptional activation and enhancing the expression of a characteristic set of genes that drive leukemogenesis. The interaction between AF9 and DOT1L is mediated by an intrinsically disordered C-terminal ANC1 homology domain (AHD) in AF9, which undergoes folding upon binding of DOT1L and other partner proteins. We have recently reported peptidomimetics that disrupt the recruitment of DOT1L by AF9 and ENL, providing a proof-of-concept for targeting AHD and assessing its druggability. Intrinsically disordered proteins, such as AF9 AHD, are difficult to study and characterize experimentally on a structural level. In this study, we present a successful protein engineering strategy to facilitate structural investigation of the intrinsically disordered AF9 AHD domain in complex with peptidomimetic inhibitors by using maltose binding protein (MBP) as a crystallization chaperone connected with linkers of varying flexibility and length. The strategic incorporation of disulfide bonds provided diffraction-quality crystals of the two disulfide-bridged MBP-AF9 AHD fusion proteins in complex with the peptidomimetics. These successfully determined first series of 2.1-2.6 Å crystal complex structures provide high-resolution insights into the interactions between AHD and its inhibitors, shedding light on the role of AHD in recruiting various binding partner proteins. We show that the overall complex structures closely resemble the reported NMR structure of AF9 AHD/DOT1L with notable difference in the conformation of the ß-hairpin region, stabilized through conserved hydrogen bonds network. These first series of AF9 AHD/peptidomimetics complex structures are providing insights of the protein-inhibitor interactions and will facilitate further development of novel inhibitors targeting the AF9/ENL AHD domain.


Assuntos
Peptidomiméticos , Peptidomiméticos/química , Peptidomiméticos/metabolismo , Humanos , Proteínas Intrinsicamente Desordenadas/química , Proteínas Intrinsicamente Desordenadas/metabolismo , Proteínas Intrinsicamente Desordenadas/genética , Proteínas Intrinsicamente Desordenadas/antagonistas & inibidores , Histona-Lisina N-Metiltransferase/química , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Modelos Moleculares , Proteínas de Fusão Oncogênica/química , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Cristalografia por Raios X , Domínios Proteicos , Proteína de Leucina Linfoide-Mieloide/química , Proteína de Leucina Linfoide-Mieloide/metabolismo , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/antagonistas & inibidores
5.
Talanta ; 276: 126292, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38795646

RESUMO

In recent decades, analytical techniques have increasingly focused on the precise quantification. Achieving this goal has been accomplished with conventional analytical approaches that typically require extensive pretreatment methods, significant reagent usage, and expensive instruments. The need for rapid, simple, and highly selective identification platforms has become increasingly pronounced. Molecularly imprinted polymer (MIP) has emerged as a promising avenue for developing advanced sensors that can potentially surpass the limitations of conventional detection methods. In recent years, the application of MIP-silica materials-based sensors has garnered significant attention owing to their distinctive characteristics. These types of probes hold a distinct advantage in their remarkable stability and durability, all of which provide a suitable sensing platform in severe environments. Moreover, the substrate composed of silica materials offers a vast surface area for binding, thereby facilitating the efficient detection of even minuscule concentrations of targets. As a result, sensors based on MIP-silica materials have the potential to be widely applied in various industries, including medical diagnosis, and food safety. In the present review, we have conducted an in-depth analysis of the latest research developments in the field of MIPs-silica materials based sensors, with a focus on succinctly summarizing and elucidating the most crucial findings. This is the first comprehensive review of integration MIPs with silica materials in electrochemical (EC) and optical probes for biomedical analysis and food safety.

6.
Drug Deliv ; 31(1): 2337423, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38590120

RESUMO

The present study was designed to develop a self-micellizing solid dispersion (SMSD) containing Thymoquinone (TQM), a phytonutrient obtained from Nigella sativa seeds, aiming to improve its biopharmaceutical and nephroprotective functions. The apparent solubility of TQM in polymer solutions was used to choose an appropriate amphiphilic polymer that could be used to make an SMSD system. Based on the apparent solubility, Soluplus® was selected as an appropriate carrier, and mixing with TQM, SMSD-TQM with different loadings of TQM (5-15%) was made by solvent evaporation and freeze-drying techniques, respectively, and the formulations were optimized. The optimized SMSD-TQM was evaluated in terms of particle size distribution, morphology, release characteristics, pharmacokinetic behavior, and nephroprotective effects in a rat model of acute kidney injury. SMSD-TQM significantly improved the dissolution characteristics (97.8%) of TQM in water within 60 min. Oral administration of SMSD-TQM in rats exhibited a 4.9-fold higher systemic exposure than crystalline TQM. In a cisplatin-induced (6 mg/kg, i.p.) acute kidney-damaged rat model, oral SMSD-TQM (10 mg/kg) improved the nephroprotective effects of TQM based on the results of kidney biomarkers and histological abnormalities. These findings suggest that SMSD-TQM might be efficacious in enhancing the nephroprotective effect of TQM by overcoming biopharmaceutical limitations.


Assuntos
Produtos Biológicos , Micelas , Ratos , Animais , Ratos Sprague-Dawley , Benzoquinonas , Solubilidade , Administração Oral , Disponibilidade Biológica
7.
Endocrinology ; 165(5)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38578954

RESUMO

In the classical insulin target tissues of liver, muscle, and adipose tissue, chronically elevated levels of free fatty acids (FFA) impair insulin signaling. Insulin signaling molecules are also present in ß-cells where they play a role in ß-cell function. Therefore, inhibition of the insulin/insulin-like growth factor 1 pathway may be involved in fat-induced ß-cell dysfunction. To address the role of ß-cell insulin resistance in FFA-induced ß-cell dysfunction we co-infused bisperoxovanadate (BPV) with oleate or olive oil for 48 hours in rats. BPV, a tyrosine phosphatase inhibitor, acts as an insulin mimetic and is devoid of any antioxidant effect that could prevent ß-cell dysfunction, unlike most insulin sensitizers. Following fat infusion, rats either underwent hyperglycemic clamps for assessment of ß-cell function in vivo or islets were isolated for ex vivo assessment of glucose-stimulated insulin secretion (GSIS). We also incubated islets with oleate or palmitate and BPV for in vitro assessment of GSIS and Akt (protein kinase B) phosphorylation. Next, mice with ß-cell specific deletion of PTEN (phosphatase and tensin homolog; negative regulator of insulin signaling) and littermate controls were infused with oleate for 48 hours, followed by hyperglycemic clamps or ex vivo evaluation of GSIS. In rat experiments, BPV protected against fat-induced impairment of ß-cell function in vivo, ex vivo, and in vitro. In mice, ß-cell specific deletion of PTEN protected against oleate-induced ß-cell dysfunction in vivo and ex vivo. These data support the hypothesis that ß-cell insulin resistance plays a causal role in FFA-induced ß-cell dysfunction.


Assuntos
Resistência à Insulina , Células Secretoras de Insulina , PTEN Fosfo-Hidrolase , Animais , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Ratos , Camundongos , Masculino , PTEN Fosfo-Hidrolase/metabolismo , Ácido Oleico/farmacologia , Insulina/metabolismo , Camundongos Endogâmicos C57BL , Secreção de Insulina/efeitos dos fármacos , Ácidos Graxos não Esterificados/metabolismo , Ratos Sprague-Dawley
8.
PLoS Negl Trop Dis ; 18(4): e0012134, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38669211

RESUMO

BACKGROUND: Currently available treatment options are mostly effective in achieving long-term cure in visceral leishmaniasis (VL) patients. However, there have been reports of recurrence of this illness in both immunosuppressed and immunocompetent patients. CASE PRESENTATION: We report the first case of recurrent VL relapse in a 19-year-old immunocompetent female with functional hypopituitarism (hypogonadotropic hypogonadism with central hypothyroidism) from Bangladesh, who has been treated three times previously with optimal dosage and duration- liposomal amphotericin B (LAmB) alone and in combination with miltefosine. We treated the patient successfully with a modified treatment regimen of 10 mg/kg body weight LAmB for two consecutive days along with oral miltefosine for seven days as loading dose. For secondary prophylaxis, the patient received 3 mg/kg body weight LAmB along with oral miltefosine for seven days monthly for five doses followed by hormonal replacement. The patient remained relapse free after 12 months of her treatment completion. CONCLUSION: In the absence of protective vaccines against Leishmania species and standard treatment regimen, this modified treatment regimen could help the management of recurrent relapse cases.


Assuntos
Anfotericina B , Antiprotozoários , Hipopituitarismo , Leishmaniose Visceral , Fosforilcolina , Recidiva , Feminino , Humanos , Adulto Jovem , Anfotericina B/uso terapêutico , Anfotericina B/administração & dosagem , Antiprotozoários/uso terapêutico , Antiprotozoários/administração & dosagem , Bangladesh , Hipopituitarismo/tratamento farmacológico , Leishmaniose Visceral/tratamento farmacológico , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapêutico , Fosforilcolina/administração & dosagem , Resultado do Tratamento , Adulto
9.
BMC Cancer ; 24(1): 441, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38594604

RESUMO

BACKGROUND: We recently found that epiplakin 1 (EPPK1) alterations were present in 12% of lung adenocarcinoma (LUAD) cases and were associated with a poor prognosis in early-stage LUAD when combined with other molecular alterations. This study aimed to identify a probable crucial role for EPPK1 in cancer development. METHODS: EPPK1 mRNA and protein expression was analyzed with clinical variables. Normal bronchial epithelial cell lines were exposed to cigarette smoke for 16 weeks to determine whether EPPK1 protein expression was altered after exposure. Further, we used CRISPR-Cas9 to knock out (KO) EPPK1 in LUAD cell lines and observed how the cancer cells were altered functionally and genetically. RESULTS: EPPK1 protein expression was associated with smoking and poor prognosis in early-stage LUAD. Moreover, a consequential mesenchymal-to-epithelial transition was observed, subsequently resulting in diminished cell proliferation and invasion after EPPK1 KO. RNA sequencing revealed that EPPK1 KO induced downregulation of 11 oncogenes, 75 anti-apoptosis, and 22 angiogenesis genes while upregulating 8 tumor suppressors and 12 anti-cell growth genes. We also observed the downregulation of MYC and upregulation of p53 expression at both protein and RNA levels following EPPK1 KO. Gene ontology enrichment analysis of molecular functions highlighted the correlation of EPPK1 with the regulation of mesenchymal cell proliferation, mesenchymal differentiation, angiogenesis, and cell growth after EPPK1 KO. CONCLUSIONS: Our data suggest that EPPK1 is linked to smoking, epithelial to mesenchymal transition, and the regulation of cancer progression, indicating its potential as a therapeutic target for LUAD.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Transição Epitelial-Mesenquimal/genética , Prognóstico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/patologia , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral
10.
Sci Adv ; 10(17): eadk3852, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38657063

RESUMO

Many insect pests, including the brown planthopper (BPH), undergo windborne migration that is challenging to observe and track. It remains controversial about their migration patterns and largely unknown regarding the underlying genetic basis. By analyzing 360 whole genomes from around the globe, we clarify the genetic sources of worldwide BPHs and illuminate a landscape of BPH migration showing that East Asian populations perform closed-circuit journeys between Indochina and the Far East, while populations of Malay Archipelago and South Asia undergo one-way migration to Indochina. We further find round-trip migration accelerates population differentiation, with highly diverged regions enriching in a gene desert chromosome that is simultaneously the speciation hotspot between BPH and related species. This study not only shows the power of applying genomic approaches to demystify the migration in windborne migrants but also enhances our understanding of how seasonal movements affect speciation and evolution in insects.


Assuntos
Migração Animal , Genômica , Vento , Animais , Genômica/métodos , Hemípteros/genética , Genoma de Inseto , Genética Populacional
11.
Mol Neurobiol ; 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38520611

RESUMO

Parkinson's disease (PD) is one of the most prevalent diseases of central nervous system that is caused by degeneration of the substantia nigra's dopamine-producing neurons through apoptosis. Apoptosis is regulated by initiators' and executioners' caspases both in intrinsic and extrinsic pathways, further resulting in neuronal damage. In that context, targeting apoptosis appears as a promising therapeutic approach for treating neurodegenerative diseases. Non-coding RNAs-more especially, microRNAs, or miRNAs-are a promising target for the therapy of neurodegenerative diseases because they are essential for a number of cellular processes, including signaling, apoptosis, cell proliferation, and gene regulation. It is estimated that a substantial portion of coding genes (more than 60%) are regulated by miRNAs. These small regulatory molecules can have wide-reaching consequences on cellular processes like apoptosis, both in terms of intrinsic and extrinsic pathways. Furthermore, it was recommended that a disruption in miRNA expression levels could also result in perturbation of typical apoptosis pathways, which may be a factor in certain diseases like PD. The latest research on miRNAs and their impact on neural cell injury in PD models by regulating the apoptosis pathway is summarized in this review article. Furthermore, the importance of lncRNA/circRNA-miRNA-mRNA network for regulating apoptosis pathways in PD models and treatment is explored. These results can be utilized for developing new strategies in PD treatment.

12.
Colloids Surf B Biointerfaces ; 235: 113768, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325142

RESUMO

Cancer is still one of the deadliest diseases, and diagnosing and treating it effectively remains difficult. As a result, advancements in earlier detection and better therapies are urgently needed. Conventional chemotherapy induces chemoresistance, has non-specific toxicity, and has a meager efficacy. Natural materials like nanosized clay mineral formations of various shapes (platy, tubular, spherical, and fibrous) with tunable physicochemical, morphological, and structural features serve as potential templates for these. As multifunctional biocompatible nanocarriers with numerous applications in cancer research, diagnosis, and therapy, their submicron size, individual morphology, high specific surface area, enhanced adsorption ability, cation exchange capacity, and multilayered organization of 0.7-1 nm thick single sheets have attracted significant interest. Kaolinite, halloysite, montmorillonite, laponite, bentonite, sepiolite, palygorskite, and allophane are the most typical nanoclay minerals explored for cancer. These multilayered minerals can function as nanocarriers to effectively carry a variety of anticancer medications to the tumor site and improve their stability, dispersibility, sustained release, and transport. Proteins and DNA/RNA can be transported using nanoclays with positive and negative surfaces. The platform for phototherapeutic agents can be nanoclays. Clays with bio-functionality have been developed using various surface engineering techniques, which could help treat cancer. The promise of nanoclays as distinctive crystalline materials with applications in cancer research, diagnostics, and therapy are examined in this review.


Assuntos
Bentonita , Neoplasias , Humanos , Bentonita/química , Caulim , Argila , Minerais , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico
13.
Microbiol Res ; 281: 127605, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38232495

RESUMO

Spermidine is a poly-cationic molecule belonging to the family of polyamines and is ubiquitously present in all organisms. Salmonella synthesizes, and harbours specialized transporters to import spermidine. A group of polyamines have been shown to assist in Salmonella Typhimurium's virulence and regulation of Salmonella pathogenicity Inslad 1 (SPI-1) genes and stress resistance; however, the mechanism remains elusive. The virulence trait of Salmonella depends on its ability to employ multiple surface structures to attach and adhere to the surface of the target cells before invasion and colonization of the host niche. Our study discovers the mechanism by which spermidine assists in the early stages of Salmonella pathogenesis. For the first time, we report that Salmonella Typhimurium regulates spermidine transport and biosynthesis processes in a mutually inclusive manner. Using a mouse model, we show that spermidine is critical for invasion into the murine Peyer's patches, which further validated our in vitro cell line observation. We show that spermidine controls the mRNA expression of fimbrial (fimA) and non-fimbrial adhesins (siiE, pagN) in Salmonella and thereby assists in attachment to host cell surfaces. Spermidine also regulated the motility through the expression of flagellin genes by enhancing the translation of sigma-28, which features an unusual start codon and a poor Shine-Dalgarno sequence. Besides regulating the formation of the adhesive structures, spermidine tunes the expression of the two-component system BarA/SirA to regulate SPI-1 encoded genes. Thus, our study unravels a novel regulatory mechanism by which spermidine exerts critical functions during Salmonella Typhimurium pathogenesis.


Assuntos
Salmonella typhimurium , Espermidina , Animais , Camundongos , Salmonella typhimurium/metabolismo , Espermidina/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Flagelina/genética , Poliaminas/metabolismo , Regulação Bacteriana da Expressão Gênica
14.
Pathol Res Pract ; 254: 155050, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199132

RESUMO

Despite great advances in diagnostic and treatment options for cancer, like chemotherapy surgery, and radiation therapy it continues to remain a major global health concern. Further research is necessary to find new biomarkers and possible treatment methods for cancer. MicroRNAs (miRNAs), tiny non-coding RNAs found naturally in the body, can influence the activity of several target genes. These genes are often disturbed in diseases like cancer, which perturbs functions like differentiation, cell division, cell cycle, apoptosis and proliferation. MiR-146a is a commonly and widely used miRNA that is often overexpressed in malignant tumors. The expression of miR-146a has been correlated with many pathological and physiological changes in cancer cells, such as the regulation of various cell death paths. It's been established that the control of cell death pathways has a huge influence on cancer progression. To improve our understanding of the interrelationship between miRNAs and cancer cell apoptosis, it's necessary to explore the impact of miRNAs through the alteration in their expression levels. Research has demonstrated that the appearance and spread of cancer can be mitigated by moderating the expression of certain miRNA - a commencement of treatment that presents a hopeful approach in managing cancer. Consequently, it is essential to explore the implications of miR-146a with respect to inducing different forms of tumor cell death, and evaluate its potential to serve as a target for improved chemotherapy outcomes. Through this review, we provide an outline of miR-146a's biogenesis and function, as well as its significant involvement in apoptosis. As well, we investigate the effects of exosomal miR-146a on the promotion of apoptosis in cancer cells and look into how it could possibly help combat chemotherapeutic resistance.


Assuntos
MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose/genética , Neoplasias/genética , Biomarcadores
15.
Plants (Basel) ; 13(2)2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38256718

RESUMO

Urbanization and associated forest conversions have given rise to a continuum of native (forest fragments) and modified (artificial grasslands and perennial ecosystems) land-use types. However, little is known about how these shifts affect soil and fine-root compartments that are critical to a functioning carbon and nutrient circulation system. In this study, soil physicochemical properties, fine-root mass, and vertical distribution patterns were investigated in four representative urban land-use types: grassland (ZJ), perennial agroecosystem (MP), broadleaf deciduous forest patch (QA), and coniferous evergreen forest patch (PD). We quantified the fine-root mass in the upper 30 cm vertical profile (0-30 cm) and at every 5 cm depth across three diameter classes (<2 mm, 2-5 mm, and <5 mm). Soil physicochemical properties, except for phosphorus, nitrogen, ammonium nitrogen, and sodium cations, varied significantly across land-use types. The total root biomass (<5 mm) decreased in the order of QA (700.3 g m-2) > PD (487.2 g m-2) > ZJ (440.1 g m-2) > MP (98.3 g m-2). The fine-root mass of ZJ and MP was correlated with soil nutrients, which was attributed to intensive management operations, while the fine-root mass of QA and PD had a significant relationship with soil organic matter due to the high inputs from forest litter. Very fine roots (<2 mm) presented a distinct decremental pattern with depth for all land-use types, except for MP. Very fine roots populated the topmost 5 cm layer in ZJ, QA, and PD at 52.1%, 49.4%, and 39.4%, respectively. Maintaining a woody fine-root system benefits urban landscapes by promoting soil stabilization, improving ground infiltration rates, and increasing carbon sequestration capacity. Our findings underscore the importance of profiling fine-root mass when assessing urban expansion effects on terrestrial ecosystems.

16.
Med Oncol ; 41(1): 41, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38165473

RESUMO

Cyclooxygenase (COX) enzymes are pivotal in inflammation and cancer development. COX-2, in particular, has been implicated in tumor growth, angiogenesis, and immune evasion. Recently, COX-2 inhibitors have arisen as potential therapeutic agents in cancer treatment. In addition, combining COX inhibitors with other treatment modalities has demonstrated the potential to improve therapeutic efficacy. This review aims to investigate the effects of COX inhibition, both alone and in combination with other methods, on signaling pathways and carcinogenesis in various cancers. In this study, a literature search of all major academic databases was conducted (PubMed, Scholar google), including the leading research on the mechanisms of COX-2, COX-2 inhibitors, monotherapy with COX-2 inhibitors, and combining COX-2-inhibitors with chemotherapeutic agents in tumors. The study encompasses preclinical and clinical evidence, highlighting the positive findings and the potential implications for clinical practice. According to preclinical studies, multiple signaling pathways implicated in tumor cell proliferation, survival, invasion, and metastasis can be suppressed by inhibiting COX. In addition, combining COX inhibitors with chemotherapy drugs, targeted therapies, immunotherapies, and miRNA-based approaches has enhanced anti-tumor activity. These results suggest that combination therapy has the potential to overcome resistance mechanisms and improve treatment outcomes. However, caution must be exercised when selecting and administering combination regimens. Not all combinations of COX-2 inhibitors with other drugs result in synergistic effects; some may even have unfavorable interactions. Therefore, personalized approaches that consider the specific characteristics of the cancer and the medications involved are crucial for optimizing therapeutic strategies. In conclusion, as monotherapy or combined with other methods, COX inhibition bears promise in modulating signaling pathways and inhibiting carcinogenesis in various cancers. Additional studies and well-designed clinical trials are required to completely elucidate the efficacy of COX inhibition and combination therapy in enhancing cancer treatment outcomes. This narrative review study provides a detailed summary of COX-2 monotherapy and combination targeted therapy in cancer treatment.


Assuntos
Inibidores de Ciclo-Oxigenase 2 , Neoplasias , Humanos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Ciclo-Oxigenase 2 , Terapia Combinada , Neoplasias/tratamento farmacológico , Carcinogênese
17.
Mymensingh Med J ; 33(1): 192-197, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38163792

RESUMO

Endoscopic transnasal repair of CSF rhinorrhoea is gaining popularity around the world because of its tremendous success rate but it depends on defect site, size, technique of repair, experiences of surgeon and also patient's profile. Aim of this study was to analysis of surgical outcome of endoscopic transnasal repair of CSF rhinorrhoea. A retrospective study carried out in the department of ENT and Head neck surgery at Bangabandhu Sheikh Mujib Medical University (BSMMU) from January 2018 to December 2019. Of the total of 24 patients 16(66.0%) were female and 8(33.0%) males. The commonest site of the leak was in the cribriform plate in 18(75.3%) followed by 5(20.8%) in the fovea ethmoidalis, and 1(4.0%) in the sphenoid sinus, the overall success rate of this series with first surgical procedure was 95.83% and 100.0% with a second procedure. Meticulous pre-operative evaluation, proper identification of leakage site, choice of graft materials and surgical technique are keys to attaining excellent results.


Assuntos
Rinorreia de Líquido Cefalorraquidiano , Masculino , Humanos , Feminino , Rinorreia de Líquido Cefalorraquidiano/cirurgia , Rinorreia de Líquido Cefalorraquidiano/etiologia , Estudos Retrospectivos , Universidades , Endoscopia/efeitos adversos , Endoscopia/métodos , Seio Esfenoidal
18.
Tuberculosis (Edinb) ; 145: 102478, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38218133

RESUMO

To evaluate the diagnostic performance of Xpert MTB/RIF Ultra (Ultra) for the diagnosis of extrapulmonary tuberculosis (EPTB) from different types of extrapulmonary specimens in comparison with culture and composite microbiological reference standard (CRS). A total of 240 specimens were prospectively collected from presumptive EPTB patients between July 2021-January 2022 and tested by Ultra, Xpert, culture and acid-fast bacilli (AFB) smear microscopy. Out of 240 specimens, 35.8 %, 20.8 %, 11.3 %, and 7.1 % were detected as Mycobacterium tuberculosis complex by Ultra, Xpert, culture and AFB microscopy, respectively. An additional 15.0 % cases were detected by Ultra compared to Xpert MTB/RIF (Xpert) assay. A total of 28 (11.7 %) cases were identified as 'trace' category by Ultra with indeterminate rifampicin resistance result; of which 36.4 % were clinically confirmed as EPTB. Compared to culture, the sensitivity and specificity of Ultra and Xpert were 100 % and 72.3 %; 92.6 % and 88.3 %, respectively. In comparison with CRS, these were respectively: 98.9 % and 100 %; 57.5 % and 100 %. For individual category of specimens, sensitivity of Ultra was 100 % with varying specificity. We found that Ultra was highly sensitive for the rapid diagnosis of EPTB and has extensive potential over current diagnostics in high TB burden countries, but 'trace' results should be interpreted with caution.


Assuntos
Antibióticos Antituberculose , Mycobacterium tuberculosis , Tuberculose Extrapulmonar , Tuberculose , Humanos , Rifampina/farmacologia , Rifampina/uso terapêutico , Mycobacterium tuberculosis/genética , Prevalência , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/tratamento farmacológico , Sensibilidade e Especificidade , Antibióticos Antituberculose/farmacologia , Antibióticos Antituberculose/uso terapêutico , Farmacorresistência Bacteriana/genética
19.
Cancer Metastasis Rev ; 43(1): 5-27, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37552389

RESUMO

The hypoxic environment is prominently witnessed in most solid tumors and is associated with the promotion of cell proliferation, epithelial-mesenchymal transition (EMT), angiogenesis, metabolic reprogramming, therapeutic resistance, and metastasis of tumor cells. All the effects are mediated by the expression of a transcription factor hypoxia-inducible factor-1α (HIF-1α). HIF-1α transcriptionally modulates the expression of genes responsible for all the aforementioned functions. The stability of HIF-1α is regulated by many proteins and non-coding RNAs (ncRNAs). In this article, we have critically discussed the crucial role of ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), Piwi-interacting RNAs (piRNAs), and transfer RNA (tRNA)-derived small RNAs (tsRNAs)] in the regulation of stability and expression of HIF-1α. We have comprehensively discussed the molecular mechanisms and relationship of HIF-1α with each type of ncRNA in either promotion or repression of human cancers and therapeutic resistance. We have also elaborated on ncRNAs that are in clinical examination for the treatment of cancers. Overall, the majority of aspects concerning the relationship between HIF-1α and ncRNAs have been discussed in this article.


Assuntos
MicroRNAs , Neoplasias , Humanos , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , RNA não Traduzido/genética
20.
Eur Child Adolesc Psychiatry ; 33(3): 897-907, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37115278

RESUMO

Little is known about the association between common mental disorders (CMD) and labor market integration among refugee and Swedish-born young adults. Socially disadvantaged patients such as refugees are more likely to discontinue their medication use prematurely. This study aimed to identify clusters of individuals with similar psychotropic medication patterns; and examine the relationship between cluster membership with labor market marginalization (LMM) in refugee and Swedish-born young adults with CMD. The study uses a longitudinal matched cohort aged 18-24 years with CMD diagnoses from Swedish registers covering 2006-2016. Dispensed psychotropic medications (antidepressants, antipsychotics, anxiolytics, sedative-hypnotics, mood stabilizers) were collected one year before and after CMD diagnosis. Clusters of patients with similar time courses of prescribed dosages were algorithmically identified. The association of cluster membership with subsequent LMM, (long-term sickness absence, SA, disability pension, DP, or long-term unemployment, UE) was assessed using Cox regression. Among 12,472 young adults with CMD, there were 13.9% with SA, 11.9% with DP, and 13.0% with UE during a mean follow-up of 4.1 years (SD 2.3 years). Six clusters of individuals were identified. A cluster with a sustained increase in all medication types yielded the highest hazard ratio (HR [95% CI]) 1.69 [1.34, 2.13] for SA and 2.63 [2.05, 3.38] for DP. The highest HRs of UE give a cluster with a concentrated peak in antidepressants at CMD diagnosis (HR 1.61[1.18, 2.18]). Refugees and Swedish-born showed similar associations between clusters and LMM. To prevent LMM, targeted support and early assessment of CMD treatment are needed for individuals with a sustained increase in psychotropic medication after CMD diagnosis and for refugees in high-risk clusters for UE characterized by a rapid lowering of treatment dosages, which could be an indicator for premature medication discontinuation.


Assuntos
Transtornos Mentais , Refugiados , Humanos , Adulto Jovem , Suécia/epidemiologia , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Transtornos Mentais/complicações , Pensões , Psicotrópicos/uso terapêutico , Antidepressivos/uso terapêutico
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