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1.
Proc Natl Acad Sci U S A ; 119(48): e2206815119, 2022 11 29.
Article in English | MEDLINE | ID: mdl-36417433

ABSTRACT

Spliceosome activation is the process of creating the catalytic site for RNA splicing and occurs de novo on each intron following spliceosome assembly. Dozens of factors bind to or are released from the activating spliceosome including the Lsm2-8 heteroheptameric ring that binds the U6 small nuclear RNA 3'-end. Lsm2-8 must be released to permit active site stabilization by the Prp19-containing complex (NineTeen Complex, NTC); however, little is known about the temporal order of events and dynamic interactions that lead up to and follow Lsm2-8 release. We have used colocalization single molecule spectroscopy (CoSMoS) to visualize Lsm2-8 dynamics during activation of Saccharomyces cerevisiae spliceosomes in vitro. Lsm2-8 is recruited as a component of the tri-snRNP and is released after integration of the Prp19-containing complex (NTC). Despite Lsm2-8 and the NTC being mutually exclusive in existing cryo-EM structures of yeast B complex spliceosomes, we identify a transient intermediate containing both ([Formula: see text]) and provide a kinetic framework for its formation and transformation during activation. Prior to [Formula: see text] assembly, the NTC rapidly and reversibly samples the spliceosome suggesting a mechanism for preventing NTC sequestration by defective spliceosomes that fail to properly activate. In complementary ensemble assays, we show that a base-pairing-dependent ternary complex can form between Lsm2-8 and U2 and U6 helix II RNAs. We propose that this interaction may play a role in formation of transient spliceosome intermediates formed during activation.


Subject(s)
Saccharomyces cerevisiae Proteins , Spliceosomes , Spliceosomes/genetics , Single Molecule Imaging , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Microscopy, Fluorescence , RNA Splicing Factors/metabolism
2.
Mod Pathol ; 37(6): 100489, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38588883

ABSTRACT

Somatic tumor testing in prostate cancer (PCa) can guide treatment options by identifying clinically actionable variants in DNA damage repair genes, including acquired variants not detected using germline testing alone. Guidelines currently recommend performing somatic tumor testing in metastatic PCa, whereas there is no consensus on the role of testing in regional disease, and the optimal testing strategy is only evolving. This study evaluates the frequency, distribution, and pathologic correlates of somatic DNA damage repair mutations in metastatic and localized PCa following the implementation of pathologist-driven reflex testing at diagnosis. A cohort of 516 PCa samples were sequenced using a custom next-generation sequencing panel including homologous recombination repair and mismatch repair genes. Variants were classified based on the Association for Molecular Pathology/American Society of Clinical Oncology/College of American Pathologists guidelines. In total, 183 (35.5%) patients had at least one variant, which is as follows: 72 of 516 (13.9%) patients had at least 1 tier I or tier II variant, whereas 111 of 516 (21.5%) patients had a tier III variant. Tier I/II variant(s) were identified in 27% (12/44) of metastatic biopsy samples and 13% (61/472) of primary samples. Overall, 12% (62/516) of patients had at least 1 tier I/II variant in a homologous recombination repair gene, whereas 2.9% (10/516) had at least 1 tier I/II variant in a mismatch repair gene. The presence of a tier I/II variant was not significantly associated with the grade group (GG) or presence of intraductal/cribriform carcinoma in the primary tumor. Among the 309 reflex-tested hormone-naive primary tumors, tier I/II variants were identified in 10% (31/309) of cases, which is as follows: 9.2% (9/98) GG2; 9% (9/100) GG3; 9.1% (4/44) GG4; and 13.4% (9/67) GG5 cases. Our findings confirm the use of somatic tumor testing in detecting variants of clinical significance in PCa and provide insights that can inform the design of testing strategies. Pathologist-initiated reflex testing streamlines the availability of the results for clinical decision-making; however, pathologic parameters such as GG and the presence of intraductal/cribriform carcinoma may not be reliable to guide patient selection.


Subject(s)
Prostatic Neoplasms , Tertiary Care Centers , Humans , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnosis , Aged , Middle Aged , Mutation , High-Throughput Nucleotide Sequencing , Pathologists
3.
Microb Pathog ; 196: 106914, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39241817

ABSTRACT

The increasing trend of antimicrobial resistance (AMR) pathogens in aquaculture makes it is imperative to find control measures for AMR pathogens causing high economic losses in aquaculture. In the present study, a multidrug resistance (MDR) Aeromonas hydrophila bacterium was isolated from kidney samples of diseased carp originating from a fish farm in Awankot, Rupnagar, Punjab, India. Moribund-infected fish exhibited large irregular hemorrhages on the external body surfaces, exophthalmia and fin-rot-like lesions. Phenotypic characterization using Rimler-Shotts (RS) media showed characteristic yellow color colonies and beta hemolysis on sheep blood agar. Genotyping using species-specific primers for the rpoB and gyrB genes characterized the isolate as A. hydrophila. The Multiple Antibiotic Resistance (MAR) index analysis showed that the isolated A. hydrophila had an MAR score of 0.29 signifying its resistance to more than three antibiotics, which underscores the need of finding treatment methods for MDR A. hydrophila isolates causing disease in aquaculture. Bacteriophages are considered a better eco-friendly alternative to antibiotics because of their inherent properties of not causing drug residues and resistance. Of the 13 phages tested, the Aeromonas veronii phage designated as AVP3, initially isolated against Aeromonas veronii, showed lytic activity against the MDR A. hydrophila isolated from diseased carp in this study. In addition, it also showed the lytic activity against Aeromonas spp. And A. caviae indicating that it had lytic properties against a wide host range within the Aeromonas species. This finding points to the potential efficacy of bacteriophages in mitigating pathogenic infections in aquaculture.

4.
Microb Pathog ; 187: 106512, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38154451

ABSTRACT

Myxozoans are obligate endoparasites, cosmopolitan in distribution with both vertebrate and invertebrate hosts. Their myxospores consist of shell valves, polar capsules with coiled polar tubules that are extrudible, and infective amoeboid germs. Myxozoan parasites are most abundant, and due to their increasing number in recent years, they can pose an emerging threat to the fish industry worldwide. Hence, the immediate need is to devise a strategy to understand and detect parasites and parasitism. They may proliferate to different organs with the advancement of infection. This all warrants the development/devising of strategies and results of integrative studies in order to identify these dreadful parasites and resolve taxonomic issues. Different methods whether classical methods including gross morphology or advanced methods such as electron microscopy (SEM, TEM, STEM), Confocal laser scanning microscopy (CLSM), histopathological studies, site preference, host and tissue specificity, a molecular approach using new markers can be clubbed for identification because these parasites are hidden and are difficult to recognize. This group was earlier classified only on the basis of myxospores morphology, but due to the high structural variability of this group advanced methods and approaches have to be implied which can minimize the problems in assigning new species.


Subject(s)
Fish Diseases , Myxozoa , Parasitic Diseases, Animal , Animals , Phylogeny , Parasitic Diseases, Animal/parasitology , Fishes/parasitology , Myxozoa/genetics , Fish Diseases/parasitology , Aquaculture
5.
Chemistry ; 30(35): e202400411, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38640109

ABSTRACT

Nicotinamide adenine dinucleotide (NAD+) is a redox active molecule that is universally found in biology. Despite the importance and simplicity of this molecule, few reports exist that investigate which molecular features are important for the activity of this ribodinucleotide. By exploiting the nonenzymatic reduction and oxidation of NAD+ by pyruvate and methylene blue, respectively, we were able to identify key molecular features necessary for the intrinsic activity of NAD+ through kinetic analysis. Such features may explain how NAD+ could have been selected early during the emergence of life. Simpler molecules, such as nicotinamide, that lack an anomeric carbon are incapable of accepting electrons from pyruvate. The phosphate moiety inhibits activity in the absence of metal ions but facilitates activity at physiological pH and model prebiotic conditions by recruiting catalytic Mg2+. Reduction proceeds through consecutive single electron transfer events. Of the derivatives tested, including nicotinamide mononucleotide, nicotinamide riboside, 3-(aminocarbonyl)-1-(2,3-dihydroxypropyl)pyridinium, 1-methylnicotinamide, and nicotinamide, only NAD+ and nicotinamide mononucleotide would be capable of efficiently accepting and donating electrons within a nonenzymatic electron transport chain. The data are consistent with early metabolic chemistry exploiting NAD+ or nicotinamide mononucleotide and not simpler molecules.


Subject(s)
Magnesium , NAD , Niacinamide , Oxidation-Reduction , NAD/chemistry , NAD/metabolism , Magnesium/chemistry , Niacinamide/chemistry , Niacinamide/analogs & derivatives , Binding Sites , Kinetics , Nicotinamide Mononucleotide/chemistry , Nicotinamide Mononucleotide/metabolism , Pyridinium Compounds/chemistry , Methylene Blue/chemistry , Pyruvic Acid/chemistry , Pyruvic Acid/metabolism , Electron Transport
6.
Mol Pharm ; 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39290162

ABSTRACT

Hydrogels, composed of hydrophilic polymer networks, have emerged as versatile materials in biomedical applications due to their high water content, biocompatibility, and tunable properties. They mimic natural tissue environments, enhancing cell viability and function. Hydrogels' tunable physical properties allow for tailored antibacterial biomaterial, wound dressings, cancer treatment, and tissue engineering scaffolds. Their ability to respond to physiological stimuli enables the controlled release of therapeutics, while their porous structure supports nutrient diffusion and waste removal, fostering tissue regeneration and repair. In wound healing, hydrogels provide a moist environment, promote cell migration, and deliver bioactive agents and antibiotics, enhancing the healing process. For cancer therapy, they offer localized drug delivery systems that target tumors, minimizing systemic toxicity and improving therapeutic efficacy. Ocular therapy benefits from hydrogels' capacity to form contact lenses and drug delivery systems that maintain prolonged contact with the eye surface, improving treatment outcomes for various eye diseases. In mucosal delivery, hydrogels facilitate the administration of therapeutics across mucosal barriers, ensuring sustained release and the improved bioavailability of drugs. Tissue regeneration sees hydrogels as scaffolds that mimic the extracellular matrix, supporting cell growth and differentiation for repairing damaged tissues. Similarly, in bone regeneration, hydrogels loaded with growth factors and stem cells promote osteogenesis and accelerate bone healing. This article highlights some of the recent advances in the use of hydrogels for various biomedical applications, driven by their ability to be engineered for specific therapeutic needs and their interactive properties with biological tissues.

7.
Soft Matter ; 20(9): 2008-2016, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38328899

ABSTRACT

Finding the best strategy to minimize the time needed to find a given target is a crucial task both in nature and in reaching decisive technological advances. By considering learning agents able to switch their dynamics between standard and active Brownian motion, here we focus on developing effective target-search behavioral policies for microswimmers navigating a homogeneous environment and searching for targets of unknown position. We exploit projective simulation, a reinforcement learning algorithm, to acquire an efficient stochastic policy represented by the probability of switching the phase, i.e. the navigation mode, in response to the type and the duration of the current phase. Our findings reveal that the target-search efficiency increases with the particle's self-propulsion during the active phase and that, while the optimal duration of the passive case decreases monotonically with the activity, the optimal duration of the active phase displays a non-monotonic behavior.

8.
Prostaglandins Other Lipid Mediat ; 175: 106887, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39243880

ABSTRACT

BACKGROUND & AIMS: Taking into account the anti-inflammatory and antioxidant properties of omega-3 fatty acids and the evidence indicating the role of chronic inflammation and oxidative stress in the pathophysiology diabetes, this study aimed to determine the effect of ω-3 fatty acids on oxidative stress and inflammatory markers in Type 2 diabetes mellitus (T2DM) patients. METHODS: A systematic search up to July 30, 2023 was completed in Scopus, PubMed, Web of Science, and Embase databases, to identify eligible RCTs. Heterogeneity tests of the selected studies were performed using the I2. Random effects models were assessed and pooled data were determined as standardized mean differences (SMD) with a 95 % CI. RESULTS: The meta-analysis of 23 trials, involving 1523 patients, demonstrated a significant decrease in TNF-α (SMD: -1.62, 95 % CI: -2.89 to -0.35, P= 0.013) and increase in TAC (SMD: 0.92, 95 % CI: 0.33-1.52, P = 0.002) following ω-3 fatty acids administration. Meanwhile, supplementation did not have beneficial effects on malondialdehyde, C-reactive protein (CRP), superoxide dismutase (SOD), and interlukin-6 levels. The subgroup analysis revealed a significant decrease in CRP levels and an increase in SOD levels in studies with durations of less than 12 weeks. CONCLUSIONS: We found that ω-3 fatty acid intake can significantly decrease TNF-α and increase TAC levels, but this effect was not observed on other markers. Nevertheless, future well-designed with large sample size and long duration RCT studies with precise ω-3 fatty acids dose and ingredients are required to understand better the effects of these compounds and their constituents on oxidative stress and inflammatory markers in T2DM patients.

9.
AIDS Behav ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39046611

ABSTRACT

We describe a provider-focused intervention to increase universal HIV testing among adolescent users in a network of School-Based Health Centers (SBHC) and compare the rate of HIV test offer and acceptance for SBHCs with and without the HIV testing intervention. The intervention was implemented at the six largest SBHCs in the 12-site network and included system- and staff-level initiatives, including an implementation coach to support SBHC associates. Rates of HIV test offer and acceptance at six sites in the Intervention Cohort were compared to that at the six sites in a Non-Intervention Cohort which was not randomly selected but had comparable distributions by age, gender and race/ethnicity. The model showed an intervention effect for universal HIV test offer, but no overall effect for test acceptance. Analyzing the intervention effect by whether a patient had a history of sexual activity, the intervention was very effective early in its implementation at increasing test offer to those with no history of sexual activity, and late in its implementation at increasing test acceptance for those with no or unknown sexual activity. Increasing and sustaining universal HIV testing in SBHCs may benefit from using Implementation Science frameworks to guide adaptation of the intervention.

10.
BMC Infect Dis ; 24(1): 651, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38943048

ABSTRACT

BACKGROUND: Respiratory viral illnesses among children are a prominent cause of morbidity and mortality in the developing world. The aim of this study is to understand the seasonal pattern and surge of respiratory viruses among the Nicobarese tribe. METHODS: Respiratory specimens were collected from both ARI and SARI cases attended the BJR district hospital in Car Nicobar Island, India, between 2021 and 2022. Respiratory viruses were identified from the specimens by using the qRT-PCR assay. Meteorological parameters were collected and evaluated using Microsoft Excel and SPSS 21. The significant association between the surge of respiratory viruses and each climatic parameter was evaluated. RESULTS: In this hospital-based cross-sectional study, 471 ILI cases were enrolled, and 209 of these were positive for respiratory viral infections. Of these respiratory virus infections, 201 (96.2%) were infected with a single respiratory virus infection, and 8 (3.8%) had mixed viral infections. Fever, cough, and chills were the most common symptoms of respiratory illness among this indigenous population. There was a significant link between respiratory viruses and influenza-like illness in children (below 5 years and 6 to 15 years). CONCLUSION: This prevalence study revealed that viral respiratory infections were more common in children than adults. Among these respiratory viruses, respiratory syncytial virus A (RSV) and influenza B virus were predominantly reported among tribal children up to age five years. In the year 2021, these viruses were recorded frequently during the winter season. Climate factors such as high humidity, high precipitation, moderate temperature, and moderate rainfall are found to be correlated with respiratory viral infections. This study implicates important information for preventing a further outbreak of respiratory viral infections in Car Nicobar Island.


Subject(s)
Respiratory Tract Infections , Seasons , Humans , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , India/epidemiology , Child , Child, Preschool , Adolescent , Cross-Sectional Studies , Female , Male , Adult , Infant , Indigenous Peoples/statistics & numerical data , Young Adult , Virus Diseases/epidemiology , Virus Diseases/virology , Viruses/classification , Viruses/isolation & purification , Viruses/genetics , Prevalence , Middle Aged
11.
J Biochem Mol Toxicol ; 38(6): e23719, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38764138

ABSTRACT

Cancer stem cells (CSCs) are associated with the tumor microenvironment (TME). CSCs induce tumorigenesis, tumor recurrence and progression, and resistance to standard therapies. Indeed, CSCs pose an increasing challenge to current cancer therapy due to their stemness or self-renewal properties. The molecular and cellular interactions between heterogeneous CSCs and surrounding TME components and tumor-supporting immune cells show synergistic effects toward treatment failure. In the immunosuppressive TME, CSCs express various immunoregulatory proteins, growth factors, metabolites and cytokines, and also produce exosomes, a type of extracellular vesicles, to protect themselves from host immune surveillance. Among these, the identification and application of CSC-derived exosomes could be considered for the development of therapeutic approaches to eliminate CSCs or cancer, in addition to targeting the modulators that remodel the composition of the TME, as reviewed in this study. Here, we introduce the role of CSCs and how their interaction with TME complicates immunotherapies, and then present the CSC-based immunotherapy and the limitation of these therapies. We describe the biology and role of tumor/CSC-derived exosomes that induce immune suppression in the TME, and finally, introduce their potentials for the development of CSC-based targeted immunotherapy in the future.


Subject(s)
Dendritic Cells , Exosomes , Immune Checkpoint Inhibitors , Immunotherapy , Neoplastic Stem Cells , Tumor Microenvironment , Humans , Exosomes/immunology , Exosomes/metabolism , Neoplastic Stem Cells/immunology , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Immunotherapy/methods , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Dendritic Cells/immunology , Dendritic Cells/metabolism , Receptors, Chimeric Antigen/immunology , Neoplasms/immunology , Neoplasms/therapy , Cancer Vaccines/immunology , Animals
12.
Environ Res ; 259: 119534, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38960361

ABSTRACT

This study presents a novel blend of synthesis techniques for shape-controlled ZnS nanoparticles. Zinc sulfide (ZnS) nanoparticles with distinct morphologies cauliflower-like microstructures (∼4.5 µm) and uniform nanospheres (200-700 nm) were synthesized through an innovative blend of precipitation and hydrothermal techniques. Capping with polyvinylpyrrolidone (PVP) significantly decreased crystallite size (3.93 nm-2.36 nm), modulated the band gap (3.57 eV-3.71 eV), and dramatically influenced morphology, highlighting the novelty of shape-controlled synthesis and its impact on optoelectronic and functional properties. X-ray diffraction confirmed crystallinity and revealed the size-controlling influence of PVP. UV-vis spectroscopy suggested potential tuning of optical properties due to band gap widening upon PVP capping. Field-emission scanning electron microscopy (FESEM) unveiled distinct morphologies: cauliflower-like microstructures for ZnS and uniform nanospheres (200-700 nm) for PVP-ZnS. Both structures were composed of smaller spherical nanoparticles, demonstrating the role of PVP in promoting controlled growth and preventing agglomeration. High-resolution transmission electron microscope (HRTEM) images depicted that the majority of nanoparticles maintain a spherical shape, though slight deviations from perfect sphericity can be discerned. Fourier-transform infrared (FTIR) spectroscopy confirmed that successful PVP encapsulation is crucial for shaping nanospheres and minimizing aggregation through steric hindrance. Photocatalytic activity evaluation using methylene blue (MB) dye degradation revealed significantly faster degradation by PVP-ZnS under ultraviolet (UV) irradiation (within 60 min as compared to 120 min for ZnS), showcasing its superior performance. This improvement can be attributed to the smaller size, higher surface area, and potentially optimized band gap of PVP-ZnS. Additionally, PVP-ZnS exhibited promising antibacterial activity against S. aureus and P. aeruginosa, with increased activity at higher nanoparticle concentrations.


Subject(s)
Anti-Bacterial Agents , Sulfides , Zinc Compounds , Zinc Compounds/chemistry , Sulfides/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Wastewater/chemistry , Chemical Precipitation , Povidone/chemistry , Water Purification/methods , Nanostructures/chemistry
13.
Int J Gynecol Cancer ; 34(6): 926-934, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38123189

ABSTRACT

Choriocarcinoma is a highly vascular and invasive tumor of anaplastic trophoblast, predominantly made up of cytotrophoblasts and syncytiotrophoblasts without villi. Based on its origin, choriocarcinoma can be either gestational or non-gestational. Non-gestational choriocarcinoma can be of germ cell origin, or can be seen in association with a somatic high-grade malignancy. It is difficult to differentiate gestational from non-gestational choriocarcinoma, especially in the reproductive age group. It is important to distinguish between the two, for accurate staging and prognostication, deciding the primary treatment modality, (ie, surgery or chemotherapy), and tailoring follow-up timeframes after diagnosis. An extensive literature search was performed regarding all cases of non-gestational choriocarcinoma, published before March 2023. A note was made of whether the origin of choriocarcinoma was ascertained and how gestational choriocarcinoma was differentiated from non-gestational choriocarcinoma. The keywords used for literature search were "non-gestational choriocarcinoma", "primary choriocarcinoma", "ovarian choriocarcinoma", "ovarian germ cell tumors", or "choriocarcinomatous differentiation". This review aims to summarize the similarities and differences in the epidemiology, pathogenesis, clinical presentation, and management guidelines between gestational and non-gestational choriocarcinoma, which can form an important educational resource for clinicians and laboratory physicians dealing with such cases.


Subject(s)
Choriocarcinoma, Non-gestational , Humans , Female , Pregnancy , Choriocarcinoma, Non-gestational/diagnosis , Choriocarcinoma, Non-gestational/pathology , Choriocarcinoma, Non-gestational/therapy , Choriocarcinoma/diagnosis , Choriocarcinoma/pathology , Choriocarcinoma/therapy , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Uterine Neoplasms/pathology , Uterine Neoplasms/diagnosis
14.
BMC Psychiatry ; 24(1): 35, 2024 01 09.
Article in English | MEDLINE | ID: mdl-38195413

ABSTRACT

BACKGROUND: Adolescence is an essential stage for the development of mental health, and suicide is among the leading cause of mortality for adolescents around the world. In India, the suicide rate among adolescents has been increasing in recent years. The scoping review was conducted to map the evidence and address gaps by examining the existing pattern, and trends, and identify the major risk factors of suicide among Indian adolescents. METHODS: The study was conducted as per the Arksey and O'Malley scoping review framework and the Joanna Briggs Institute Reviewers' manual. The systematic search was performed using electronic databases such as PubMed, Google Scholar, EMBASE, and PsycINFO, by using specific keywords. After the screening, 35 articles were identified according to the inclusion criteria. RESULTS: The evidence on the trends of suicide among adolescents showed that the suicide rate has shown an alarming increase in recent years. The evidence pattern showed that hanging and poisoning were the commonly selected methods used by adolescents. The most commonly reported risk factors were mental health problems (54.28%), negative or traumatic familiar issues (34.28%), academic stress (22.85%), social/lifestyle factors (20%), violence (22.85%), economic distresses (8.75%), relationship factor (8.75%). CONCLUSION: By synthesizing and summarising the patterns, trends, and key risk factors of suicide among Indian adolescents, this scoping review provides a broad understanding of the literature already in existence. In order to effectively tackle these issues, the finding highlights the urgent need for extensive and targeted suicide prevention measures.


Subject(s)
Suicide , Humans , Adolescent , Suicide Prevention , Asian People , Databases, Factual , Risk Factors
15.
Cell Biochem Funct ; 42(3): e4006, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38622913

ABSTRACT

Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long noncoding RNA (lncRNA) that is widely expressed in a variety of mammalian cell types. Altered expression levels of the lncRNA NEAT1 have been reported in liver-related disorders including cancer, fatty liver disease, liver fibrosis, viral hepatitis, and hepatic ischemia. lncRNA NEAT1 mostly acts as a competing endogenous RNA (ceRNA) to sponge various miRNAs (miRs) to regulate different functions. In regard to hepatic cancers, the elevated expression of NEAT1 has been reported to have a relation with the proliferation, migration, angiogenesis, apoptosis, as well as epithelial-mesenchymal transition (EMT) of cancer cells. Furthermore, NEAT1 upregulation has contributed to the pathogenesis of other liver diseases such as fibrosis. In this review, we summarize and discuss the molecular mechanisms by which NEAT1 contributes to liver-related disorders including acute liver failure, nonalcoholic fatty liver disease (NAFLD), liver fibrosis, and liver carcinoma, providing novel insights and introducing NEAT1 as a potential therapeutic target in these diseases.


Subject(s)
MicroRNAs , Non-alcoholic Fatty Liver Disease , RNA, Long Noncoding , Animals , Humans , Cell Proliferation/genetics , Fibrosis , Liver Cirrhosis/genetics , Mammals/genetics , Mammals/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Non-alcoholic Fatty Liver Disease/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
16.
Cell Biochem Funct ; 42(4): e4029, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38773914

ABSTRACT

Mesenchymal stem cell-derived exosomes (MSC-Exos) are emerging as remarkable agents in the field of immunomodulation with vast potential for diagnosing and treating various diseases, including cancer and autoimmune disorders. These tiny vesicles are laden with a diverse cargo encompassing proteins, nucleic acids, lipids, and bioactive molecules, offering a wealth of biomarkers and therapeutic options. MSC-Exos exhibit their immunomodulatory prowess by skillfully regulating pattern-recognition receptors (PRRs). They conduct a symphony of immunological responses, modulating B-cell activities, polarizing macrophages toward anti-inflammatory phenotypes, and fine-tuning T-cell activity. These interactions have profound implications for precision medicine, cancer immunotherapy, autoimmune disease management, biomarker discovery, and regulatory approvals. MSC-Exos promises to usher in a new era of tailored therapies, personalized diagnostics, and more effective treatments for various medical conditions. As research advances, their transformative potential in healthcare becomes increasingly evident.


Subject(s)
Exosomes , Mesenchymal Stem Cells , Receptors, Pattern Recognition , Humans , Exosomes/metabolism , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/immunology , Mesenchymal Stem Cells/cytology , Receptors, Pattern Recognition/metabolism , Animals , Immunomodulation
17.
BMC Womens Health ; 24(1): 139, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38395851

ABSTRACT

BACKGROUND: Human papillomavirus (HPV) is associated with cervical cancer and cervical dysplasia worldwide. Data on HPV prevalence in a region is important because it serves as a predictor of the likelihood of the population in that particular region acquiring cervical cancer. Moreover, with the availability of effective vaccines, the public health system must be aware of the preponderance of HPV to implement the vaccine. The present study was designed to understand the prevalence of HPV and associated factors among the women of South Andaman Island. METHODS: A cross-sectional study was conducted among married women of reproductive age (18-59 years) from South Andaman District from 2018 to 2022. Cervical scrapes were collected from participants after obtaining informed written consent for HPV molecular testing (HPV DNA) such as PCR assay. Demographic data was collected using a standard questionnaire and statistical analyses were performed to determine the associated factors. RESULTS: The study showed prevalence of HPV as 5.9%(95% CI: 3.9-7.9) and prevalence of HR-HPV16 was 4.1% (95% CI 2.6 - 5.5) and HR-HPV18 prevalence was 1.8(95% CI: 0.6-3). The independent factors associated the HPV positivity were age above 55 years, menopause, post-menopausal bleeding, blood-stained vaginal discharge and loss of weight. Age was associated with all HPV infections among the South Andaman women. CONCLUSIONS: HPV 16 was reported as the predominant high risk HPV type circulating among women of South Andaman. Cervical cancer and precancerous lesions were significantly associated with HPV positivity and High risk HPV 16. Based on the knowledge of the risk factors associated with HPV, implementation of stronger public health awareness and prophylactic HPV vaccination is crucial among the women of this remote island.


Subject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Neoplasms , Humans , Female , Adolescent , Young Adult , Adult , Middle Aged , Papillomavirus Infections/prevention & control , Uterine Cervical Neoplasms/prevention & control , Cross-Sectional Studies , Human papillomavirus 16/genetics , Risk Factors , India/epidemiology , Papillomaviridae/genetics , Prevalence , Papillomavirus Vaccines/therapeutic use
18.
J Basic Microbiol ; 64(1): 4-21, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37861279

ABSTRACT

Color serves as the initial attraction and offers a pleasing aspect. While synthetic colorants have been popular for many years, their adverse environmental and health effects cannot be overlooked. This necessitates the search for natural colorants, especially microbial colorants, which have proven and more effective. Pigment-producing microorganisms offer substantial benefits. Natural colors improve product marketability and bestow additional benefits, including antioxidant, antiaging, anticancer, antiviral, antimicrobial, and antitumor properties. This review covers the various types of microbial pigments, the methods to enhance their production, and their cosmetic and therapeutic applications. We also address the challenges faced during the commercial production of microbial pigments and propose potential solutions.


Subject(s)
Antioxidants , Pigments, Biological , Antioxidants/therapeutic use
19.
Int J Mol Sci ; 25(8)2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38674151

ABSTRACT

In response to cellular metabolic and signaling cues, the mitochondrial network employs distinct sets of membrane-shaping factors to dynamically modulate organellar structures through a balance of fission and fusion. While these organellar dynamics mediate mitochondrial structure/function homeostasis, they also directly impact critical cell-wide signaling pathways such as apoptosis, autophagy, and the integrated stress response (ISR). Mitochondrial fission is driven by the recruitment of the cytosolic dynamin-related protein-1 (DRP1), while fusion is carried out by mitofusins 1 and 2 (in the outer membrane) and optic atrophy-1 (OPA1) in the inner membrane. This dynamic balance is highly sensitive to cellular stress; when the transmembrane potential across the inner membrane (Δψm) is lost, fusion-active OPA1 is cleaved by the overlapping activity with m-AAA protease-1 (OMA1 metalloprotease, disrupting mitochondrial fusion and leaving dynamin-related protein-1 (DRP1)-mediated fission unopposed, thus causing the collapse of the mitochondrial network to a fragmented state. OMA1 is a unique regulator of stress-sensitive homeostatic mitochondrial balance, acting as a key upstream sensor capable of priming the cell for apoptosis, autophagy, or ISR signaling cascades. Recent evidence indicates that higher-order macromolecular associations within the mitochondrial inner membrane allow these specialized domains to mediate crucial organellar functionalities.


Subject(s)
Homeostasis , Metalloendopeptidases , Mitochondria , Mitochondrial Dynamics , Mitochondrial Proteins , Stress, Physiological , Humans , Animals , Mitochondria/metabolism , Mitochondrial Proteins/metabolism , Metalloendopeptidases/metabolism , Signal Transduction , Autophagy , Dynamins/metabolism , Apoptosis , GTP Phosphohydrolases/metabolism
20.
J Environ Manage ; 355: 120431, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38457890

ABSTRACT

Cover crops (CC) can improve phosphorus (P) cycling by reducing water related P losses and contributing to P nutrition of a rotational crop. This is particularly important in claypan soils with freeze-thaw cycles in early spring in the Midwest U.S. This 4-year study (2019-2022) examined the impact of CC monoculture and mix of CC species on P losses from a fertilizer application, and determined the P balance in soil compared to no cover crop (noCC). The CC mix consisted of wheat (Triticum aestivum L.), radish (Raphanus raphanistrum subsp. Sativus), and turnip (Brassica rapa subsp. Rapa) (3xCCmix) in 2019 and 2021 before corn, and cereal rye (Secale cereale L.) was planted as monoculture before soybean in 2020 and 2022. The 3xCCmix had no effect on total phosphorus (TP) and dissolved reactive phosphorus (PO4-P) concentration or load in 2019 and 2021. Cereal rye reduced TP and PO4-P load 70% and 73%, respectively, compared to noCC. The variation in soil moisture, temperature, and net precipitation from fertilizer application until CC termination affected available soil P pools due to variability in CC species P uptake, residue decomposition, and P loss in surface water runoff. Overall, the P budget calculations showed cereal rye had 2.4 kg ha-1 greater P uptake compared to the 3xCCmix species which also reduced P loss in water and had greater differences in soil P status compared to noCC. This study highlights the benefit of CCs in reducing P loss in surface runoff and immobilizing P through plant uptake. However, these effects were minimal with 3xCCmix species and variability in crop residue decomposition from different CC species could affect overall P-soil balance.


Subject(s)
Agriculture , Phosphorus , Fertilizers , Soil , Crops, Agricultural , Edible Grain , Zea mays , Secale , Water
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