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1.
SA J Radiol ; 28(1): 2766, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725971

RESUMO

Horseshoe lung (HL) is a rare congenital anomaly represented by the fusion of both lungs, posterior to the heart, and is typically associated with various bronchopulmonary and cardiovascular malformations. Multi-detector contrast enhanced CT is the imaging modality of choice to demonstrate the pathology and associated malformations. There has been inconsistency in the nomenclature used for such cases in literature. To resolve ambiguity, the authors emphasise that only two terms: HL and pseudo-HL be used on imaging to describe variants of this congenital malformation. Contribution: A description of the imaging features in four cases of HL, with their associated malformations and a review of the nomenclature.

2.
Cancers (Basel) ; 16(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38730663

RESUMO

In recent years, kaempferol, a natural flavonoid present in various fruits and vegetables, has received significant attention in gastrointestinal cancer research due to its varied therapeutic effects. Kaempferol has been proven to alter several molecular mechanisms and pathways, such as the PI3/Akt, mTOR, and Erk/MAPK pathway involved in cancer progression, showing its inhibitory effects on cell proliferation, survival, angiogenesis, metastasis, and migration. Kaempferol is processed in the liver and small intestine, but limited bioavailability has been a major concern in the clinical implications of kaempferol. Nano formulations have been proven to enhance kaempferol's efficacy in cancer prevention. The synergy of nanotechnology and kaempferol has shown promising results in in vitro studies, highlighting the importance for more in vivo research and clinical trials to determine safety and efficacy. This review aims to focus on the role of kaempferol in various types of gastrointestinal cancer and how the combination of kaempferol with nanotechnology helps in improving therapeutic efficacy in cancer treatment.

3.
Health Sci Rep ; 7(4): e2072, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38660003

RESUMO

Background: Scleroderma, also referred to as systemic sclerosis, is a multifaceted autoimmune condition characterized by abnormal fibrosis and impaired vascular function. Pathologically, it encompasses the persistent presence of inflammation, abnormal collagen buildup, and restructuring of blood vessels in various organs, resulting in a wide range of clinical symptoms. This review incorporates the most recent scientific literature on scleroderma, with a particular emphasis on its pathophysiology, clinical manifestations, diagnostic approaches, and treatment options. Methodology: A comprehensive investigation was carried out on numerous databases, such as PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar, to collect pertinent studies covering diverse facets of scleroderma research. Results: Scleroderma presents with a range of systemic manifestations, such as interstitial lung disease, gastrointestinal dysmotility, Raynaud's phenomenon, pulmonary arterial hypertension, renal complications, neurological symptoms, and cardiac abnormalities. Serological markers, such as antinuclear antibodies, anti-centromere antibodies, and anti-topoisomerase antibodies, are important for classifying diseases and predicting their outcomes. Discussion: The precise identification of scleroderma is crucial for promptly and correctly implementing effective treatment plans. Treatment approaches aim to improve symptoms, reduce complications, and slow down the progression of the disease. An integrated approach that combines pharmacological agents, including immunosuppressants, endothelin receptor antagonists, and prostanoids, with nonpharmacological interventions such as physical and occupational therapy is essential for maximizing patient care. Conclusion: Through the clarification of existing gaps in knowledge and identification of emerging trends, our goal is to improve the accuracy of diagnosis, enhance the effectiveness of therapeutic interventions, and ultimately enhance the overall quality of life for individuals suffering from scleroderma. Ongoing cooperation and creative research are necessary to advance the field and achieve improved patient outcomes and new therapeutic discoveries.

4.
Cureus ; 16(3): e55942, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38601398

RESUMO

Background Diarrhea is a major public health problem in under-five children worldwide. Various sociodemographic, environmental, and behavioral factors play a role in the occurrence of diarrheal disease in children under the age of five. This study aims to estimate the cumulative incidence of acute diarrheal diseases during a one-year study period and examine its association with the built environment factors among children under the age of five in selected underprivileged areas of Bhopal. Methodology We conducted this study in Bhopal, a city in central India. We surveyed the underprivileged dwellers of Vajpayee Nagar, Sanjay Nagar, and Mother India Colony of Bhopal city. This is a prospective cohort study with a one-year follow-up period to examine the cumulative incidence of acute diarrheal diseases among under-five-year-old children in the study area. Data were analyzed using SPSS version 25 (IBM Corp., Armonk, NY, USA). Results Data were collected from February 2021 to February 2022. A total of 658 families of eligible children were contacted to participate in the study. After excluding 38 participants for various reasons (denied consent: 3; lost to follow-up: 32; moved out of the study area: 3), data were finally analyzed for 620 participants. In the study among the under-five-year-old children, the cumulative incidence of acute diarrheal diseases was 23.8% (148 out of 620). In our study, lower age (adjusted odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.75-0.99, p = 0.041) and non-availability of flush latrine in the house (adjusted OR = 4.95, 95% CI = 1.80-13.59, p = 0.002) were statistically associated with a higher incidence of acute diarrheal disease among the study population. Conclusions In our investigation, we observed a cumulative incidence of diarrhea at 23.8% (148 out of 620) among the underprivileged under-five population residing in Bhopal, India. This incidence exhibited significant associations with younger age and the absence of in-house flush latrines.

5.
JBJS Case Connect ; 14(2)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38635780

RESUMO

CASE: A 47-year-old orthopaedic surgeon presented with acute volar left wrist pain. He performed over 250 robot-assisted knee arthroplasties each year. Color Doppler evaluation revealed bilateral persistent median arteries and bifid median nerves, with focal occlusive thrombosis of the left median artery. He was advised rest and oral aspirin. He could return to his professional activities after 1 month. He had no recurrence of symptoms at 1 year of follow-up. CONCLUSION: Orthopaedic surgeons use vibrating hand tools on a daily basis. The possibility of hand-arm vibration syndrome must be considered in the differential diagnosis of wrist pain among orthopaedic surgeons.


Assuntos
Artroplastia do Joelho , Síndrome do Túnel Carpal , Procedimentos Cirúrgicos Robóticos , Robótica , Cirurgiões , Trombose , Masculino , Humanos , Pessoa de Meia-Idade , Nervo Mediano/cirurgia , Síndrome do Túnel Carpal/cirurgia , Artérias , Trombose/etiologia , Trombose/complicações , Artralgia/cirurgia , Artroplastia do Joelho/efeitos adversos
6.
RSC Med Chem ; 15(3): 1022-1037, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38516592

RESUMO

Malaria eradication is still a global challenge due to the lack of a broadly effective vaccine and the emergence of drug resistance to most of the currently available drugs as part of the mainline artemisinin-based combination therapy. A variety of experimental approaches are quite successful in identifying and synthesizing new promising pharmacophore hybrids with distinct mechanisms of action. Based on our recent findings, the current study demonstrates the reinvestigation of a series of diphenylmethylpiperazine and pyrazine-derived molecular hybrids. Pyrazine-derived molecular hybrids were screened to investigate the antiplasmodial activity on drug-susceptible Pf3D7 and drug-resistant PfW2 strains. The selected compounds were shown to be potent dual inhibitors of cysteine protease PfFP2 and PfFP3. Time-course parasitic development study demonstrated that compounds were able to arrest the growth of the parasite at the early trophozoite stage. The compounds did not show hemolysis of red blood cells and showed selectivity to the parasite compared with the mammalian Vero and A5489 cell lines. The study underlined HR5 and HR15 as a new class of Plasmodial falcipain inhibitors with an IC50 of 6.2 µM and 5.9 µM for PfFP2 and 6.8 µM and 6.4 µM for PfFP3, respectively. Both compounds have antimalarial efficacy with IC50 values of 3.05 µM and 2.80 µM for the Pf3D7 strain, and 4.35 µM and 3.39 µM for the PfW2 strain, respectively. Further structural optimization may turn them into potential Plasmodial falcipain inhibitors for malaria therapeutics.

7.
J Interferon Cytokine Res ; 44(5): 221-231, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38530079

RESUMO

Interleukin-17A is a pro-inflammatory cytokine that plays a key role in the immune response to many pathogens and implicated in autoimmune diseases. This molecule is also involved in providing protection to many bacterial and fungal infections of gastro-intestinal tract and respiratory mucosa. Although molecular aspect of IL-17A has been studied in few species, no data are available for buffalo, which is one of the major sources of milk production in India. Therefore, in the present study, IL-17A gene of Indian Murrah Buffalo origin was cloned, expressed, and analyzed using bioinformatic tools. The coding sequence of buffalo IL-17A gene was cloned in prokaryotic expression vector (pET-28a) followed by its expression, purification, and characterization. A computational analysis was performed to understand the sequence, structure, and evolutionary relationship of buIL-17A. It revealed that the length of buIL-17A sequence without signal peptide is 132 amino acids as in cattle. However, sequence identity is found to be 99% due to one amino substitution difference between buffalo and cattle. After analysis, it can be concluded that buIL-17A recombinant protein can be used as a potential immunobiological reagent for diagnostic and therapeutic purpose.


Assuntos
Sequência de Aminoácidos , Búfalos , Interleucina-17 , Búfalos/genética , Búfalos/imunologia , Animais , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucina-17/imunologia , Interleucina-17/química , Clonagem Molecular , Filogenia , Bovinos , Modelos Moleculares , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia
8.
Immunology ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504502

RESUMO

Treatment of tuberculosis (TB) is faced with several challenges including the long treatment duration, drug toxicity and tissue pathology. Host-directed therapy provides promising avenues to find compounds for adjunctively assisting antimycobacterials in the TB treatment regimen, by promoting pathogen eradication or limiting tissue destruction. Eicosanoids are a class of lipid molecules that are potent mediators of inflammation and have been implicated in aspects of the host response against TB. Here, we have explored the blood transcriptome of pulmonary TB patients to understand the activity of leukotriene B4, a pro-inflammatory eicosanoid. Our study shows a significant upregulation in the leukotriene B4 signalling pathway in active TB patients, which is reversed with TB treatment. We have further utilized our in-house network analysis algorithm, ResponseNet, to identify potential downstream signal effectors of leukotriene B4 in TB patients including STAT1/2 and NADPH oxidase at a systemic as well as local level, followed by experimental validation of the same. Finally, we show the potential of inhibiting leukotriene B4 signalling as a mode of adjunctive host-directed therapy against TB. This study provides a new mode of TB treatment along with mechanistic insights which can be further explored in pre-clinical trials.

9.
Chempluschem ; 89(4): e202300721, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38385783

RESUMO

An easily synthesizable indole-derived chromofluorogenic probe InNS has been demonstrated for recognition of trivalent metal ions (i. e., Al3+, Ga3+, In3+ and Fe3+). Both UV-Vis and emission spectral studies have been employed to assess the cation sensing ability of InNS in semi-aqueous medium. This probe exhibited a chromogenic response for these metal ions, and the related change was accompanied with the appearance of a new absorption near 376 nm. An obvious color change from pale yellow to dark yellow could also be noticed upon addition of the aforementioned metal ions to the probe's solution. Distinctively from the UV-Vis analysis, the fluorescence behavior of InNS was completely different; it displayed a 'turn-on' fluorescence response for only Al3+ among all the studied cations. The detection limit and the association constant (Ka) for Al3+ were determined to be 12.5 nM and 6.85×106 M-1, respectively. A potential 1 : 1 binding mode of Al3+-InNS has been established based on Job's plot, 1H NMR and DFT analyses. The reversibility experiment was conducted using strongly chelating EDTA ion, and a corresponding logic gate has been devised. In terms of practical applications, the InNS has been utilized to detect Al3+ in human breast carcinoma (MCF-7) cell lines displaying promising 'turn-on' bioimaging experiments.

10.
J Biomol Struct Dyn ; : 1-12, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407814

RESUMO

The current trend in biomedical research is on prioritizing infections based on multidrug resistance. Elizabethkingia meningoseptica, a nosocomial infection-causing organism emerging from Neonatal Intensive Care Units (NICUs), leads to neonatal meningitis and sepsis resulting in severe illness, and, in some cases, fatal. Finding a solution remains challenging due to limited prior work. Translational S12 ribosomal proteins play a crucial role in decoding the codon-anticodon helix, which is essential for the survival of E. meningoseptica. These proteins do not exhibit significant similarity with humans, making them potential drug targets. An in silico study aims to identify specific inhibitors for E. meningoseptica ribosomal proteins among known bioactive compounds targeting prokaryotic 30S ribosomal protein. A 3D model of the 7JIL_h protein from Flavobacterium johnsoniae, showing 90% sequence similarity with the target protein was generated using SWISS-MODEL software. The model was validated through Molprobity v4.4, VERIFY 3D, Errata, and ProSA analysis, confirming conserved residues of the target protein. Insilico screening of known bioactive compounds and their analogs identified potential ligands for the target protein. Molecular Docking and post-docking analysis assessed the stability of the protein-ligand complexes among the shortlisted compounds. The top two compounds with high Gold fitness scores and low predicted binding energy underwent MD simulation and further estimation of free binding energy using the MM_PBSA module. These computationally shortlisted compounds, namely chEMBL 1323619 and chEMBL 312490 may be considered for future in-vivo studies as potential inhibitors against the modeled 30S ribosomal protein S12 of E. meningoseptica.Communicated by Ramaswamy H. Sarma.

11.
BMC Public Health ; 24(1): 527, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378536

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is frequently misdiagnosed during pregnancy. There is an abundance of evidence, but little is known regarding the regional prevalence estimates of GDM in India. This systematic review and meta-analysis aims to provide valuable insights into the national and regional prevalence of GDM among pregnant women in India. METHODS: We conducted an initial article search on PubMed, Scopus, Google Scholar, and ShodhGanga searches to identify quantitative research papers (database inception till 15th June,2022). This review included prevalence studies that estimated the occurrence of GDM across different states in India. RESULTS: Two independent reviewers completed the screening of 2393 articles, resulting in the identification of 110 articles that met the inclusion criteria, which collectively provided 117 prevalence estimates. Using a pooled estimate calculation (with an Inverse square heterogeneity model), the pooled prevalence of GDM in pregnant women was estimated to be 13%, with a 95% confidence interval (CI) ranging from 9 to 16%.. In India, Diabetes in Pregnancy Study of India (DIPSI) was the most common diagnostic criteria used, followed by International Association of Diabetes and Pregnancy Study Groups (IADPSG) and World Health Organization (WHO) 1999. It was observed that the rural population has slightly less prevalence of GDM at 10.0% [6.0-13.0%, I2=96%] when compared to the urban population where the prevalence of GDM was 12.0% [9.0-16.0%, I2 = 99%]. CONCLUSIONS: This review emphasizes the lack of consensus in screening and diagnosing gestational diabetes mellitus (GDM), leading to varied prevalence rates across Indian states. It thoroughly examines the controversies regarding GDM screening by analyzing population characteristics, geographic variations, diagnostic criteria agreement, screening timing, fasting vs. non-fasting approaches, cost-effectiveness, and feasibility, offering valuable recommendations for policy makers. By fostering the implementation of state-wise screening programs, it can contribute to improving maternal and neonatal outcomes and promoting healthier pregnancies across the country.


Assuntos
Diabetes Gestacional , Recém-Nascido , Gravidez , Feminino , Humanos , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Prevalência , Teste de Tolerância a Glucose , Jejum , Índia/epidemiologia , Resultado da Gravidez/epidemiologia
12.
Sci Total Environ ; 920: 171043, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38369158

RESUMO

Rapid modern industrialization and urbanization have escalated heavy metal pollution, with palladium (Pd2+) raising significant concerns due to its extensive usage in catalysis, hydrogen storage, and electronics, thereby imposing substantial risks on the environment and human health. In this study, we report a highly fluorescent indium nanocubes based chemosensor (InNCs) functionalized with perylene tetracarboxylic acid (PTCA) and 4-(pyridyl)ethenyl benzene (PEB). The InNCs exhibited emission maximum at 415 nm (λex âˆ¼ 350 nm) with robust chemical and photo-stability, and acted as a fluorogenic probe for selective recognition of Pd2+ in aqueous medium. The fluorescence sensing properties of InNCs were thoroughly assessed via different techniques including steady-state absorption, emission and time-resolved emission spectroscopic methods. Among the various competitive analytes, only Pd2+ could induce a significant fluorescence quenching in the probe. This "turn-off" fluorescence sensing demonstrated a remarkably low LoD of ∼65 nM. Notably, with the addition of EDTA, the probe displayed good recyclability upto 4 cycles. The sensory probe was successfully employed as a reusable platform to estimate Pd(II) in different real water and soil samples with considerable accuracy (∼ 5-10 % error). Moreover, the probe exhibited a pH-induced fluorescence transition, indicating its potential to be applied as a pH sensor. The Pd(II) binding and pH-sensing mechanisms have also been elucidated through density functional theory (DFT) calculations.

13.
Genetics ; 226(3)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38279937

RESUMO

Adaptation to external environmental challenges at the cellular level requires rapid responses and involves relay of information to the nucleus to drive key gene expression changes through downstream transcription factors. Here, we describe an alternative route of adaptation through a direct role for cellular signaling components in governing gene expression via RNA interference-mediated small RNA production. Calcium-calcineurin signaling is a highly conserved signaling cascade that plays central roles in stress adaptation and virulence of eukaryotic pathogens, including the human fungal pathogen Cryptococcus neoformans. Upon activation in C. neoformans, calcineurin localizes to P-bodies, membraneless organelles that are also the site for RNA processing. Here, we studied the role of calcineurin and its substrates in RNAi-mediated transgene silencing. Our results reveal that calcineurin regulates both the onset and the reversion of transgene silencing. We found that some calcineurin substrates that localize to P-bodies also regulate transgene silencing but in opposing directions. Small RNA sequencing in mutants lacking calcineurin or its targets revealed a role for calcineurin in small RNA production. Interestingly, the impact of calcineurin and its substrates was found to be different in genome-wide analysis, suggesting that calcineurin may regulate small RNA production in C. neoformans through additional pathways. Overall, these findings define a mechanism by which signaling machinery induced by external stimuli can directly alter gene expression to accelerate adaptative responses and contribute to genome defense.


Assuntos
Criptococose , Cryptococcus neoformans , Humanos , Cryptococcus neoformans/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Calcineurina/genética , Calcineurina/metabolismo , Criptococose/microbiologia , Transgenes , Proteínas Fúngicas/genética
14.
Sci Rep ; 14(1): 868, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195737

RESUMO

The present study was conducted to evaluate the genetic variability for morphological and qualitative traits of Coccinia for development of trait specific lines at ICAR-Central Horticultural Experiment Station (CIAH-RS), Panchmahals (Godhra), Gujarat during 2020-2022. In this study, we evaluated 26 gynoecious accessions to assess the genetic divergence through principal component and cluster analysis. The experiment was carried out in a randomized complete block design with three replications under rainfed semi-arid conditions. High values of PCV and GCV were observed for variables such as NFFP (25.13 and 22.20), PL (23.14 and 20.69), FD (24.01 and 21.46), AFW (22.98 and 20.13), NFPY (26.38 and 24.40), FYP (37.57 and 31.29), FY (35.55 and 33.20), AsC (28.65 and 27.73), Ac (24.32 and 21.06), TSS (37.23 and 35.94), DPPHL (20.71 and 20.38), FRAPL (21.08 and 20.92), TPF(20.81 and 20.45) respectively. High heritability coupled with high genetic advance as per cent of mean was observed for vine length (VL), internodal length (IL), number of female flowers per plant (NFFP), fruit length (FL), peduncle length (PL), fruit diameter (FD), average fruit weight (AFW), number of fruit per plant per year (NFPY), fruit yield per plant (FYP), fruit yield (FY), ascorbic acid (AsC), acidity (Ac), total soluble solids (TSS), total phenols in leaves TPL), total flavonoids in leaves TFL, CUPRAC in leaves (CUPRACL), DPPH in leaves (DPPHL), FRAP in leaves (FRAPL), Total phenols in fruits (TPF), Total flavonoids in fruits (TFF), CUPRAC in fruits (CUPRACF) and DPPH in fruits (DPPHF). The FYP exhibited a significant positive correlation with variables like VL (0.6833), IL (0.2991), NFFP (0.8107), FD (0.5245), AFW (0.6766), NFPY (0.7659), ASC (0.4611), TSS (0.5004) and TPF (0.4281). The estimates of genetic parameters revealed scope for further improvement of fruit yield by selection. Of the eight principal components, PC-I through PC-VIII had eigen values greater than 1 and it accounts 85.02% of the total variation for 26 gynoecious accessions of Ivy gourd. The eigen values of PC-I comprised 5.775% of total variation followed by PC-II (4.250%), PC-III (3.175%), PC-IV (2.588%), PC-V (1.828%), PC-VI (1.447%), PC-VII (1.179%) and PC-VIII (1.013%).The cluster VI and cluster I having highest mean values for most of traits under study. Thus, genotypes from the distinct cluster like cluster VI and I for should be used for selection of parents and varietal improvement for further breeding programme in ivy gourd.


Assuntos
Antioxidantes , Cucurbitaceae , Flavonoides , Variação Genética , Azia , Fenóis , Melhoramento Vegetal
15.
Brief Funct Genomics ; 23(1): 69-74, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36722037

RESUMO

The entire world is facing the stiff challenge of COVID-19 pandemic. To overcome the spread of this highly infectious disease, several short-sighted strategies were adopted such as the use of broad-spectrum antibiotics and antifungals. However, the misuse and/or overuse of antibiotics have accentuated the emergence of the next pandemic: antimicrobial resistance (AMR). It is believed that pathogens while transferring between humans and the environment carry virulence and antibiotic-resistant factors from varied species. It is presumed that all such genetic factors are quantifiable and predictable, a better understanding of which could be a limiting step for the progression of AMR. Herein, we have reviewed how genomics-based understanding of host-pathogen interactions during COVID-19 could reduce the non-judicial use of antibiotics and prevent the eruption of an AMR-based pandemic in future.


Assuntos
COVID-19 , Humanos , Pandemias , Interações Hospedeiro-Patógeno/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos/genética , Genômica , Farmacorresistência Bacteriana
16.
Artigo em Inglês | MEDLINE | ID: mdl-37518952

RESUMO

Protein unfolding and aggregation are often correlated with numerous diseases such as Alzheimer's, Parkinson's, Huntington's, and other debilitating neurological disorders. Such adverse events consist of a plethora of competing mechanisms, particularly interactions that control the stability and cooperativity of the process. However, it remains challenging to probe the molecular mechanism of protein dynamics such as aggregation, and monitor them in real-time under physiological conditions. Recently, Raman spectroscopy and its plasmon-enhanced counterparts, such as surface-enhanced Raman spectroscopy (SERS) and tip-enhanced Raman spectroscopy (TERS), have emerged as sensitive analytical tools that have the potential to perform molecular studies of functional groups and are showing significant promise in probing events related to protein aggregation. We summarize the fundamental working principles of Raman, SERS, and TERS as nondestructive, easy-to-perform, and fast tools for probing protein dynamics and aggregation. Finally, we highlight the utility of these techniques for the analysis of vibrational spectra of aggregation of proteins from various sources such as tissues, pathogens, food, biopharmaceuticals, and lastly, biological fouling to retrieve precise chemical information, which can be potentially translated to practical applications and point-of-care (PoC) devices. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > Diagnostic Nanodevices Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.


Assuntos
Nanotecnologia , Análise Espectral Raman , Análise Espectral Raman/métodos , Nanotecnologia/métodos
17.
bioRxiv ; 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-37546757

RESUMO

Adaptation to external environmental challenges at the cellular level requires rapid responses and involves relay of information to the nucleus to drive key gene expression changes through downstream transcription factors. Here, we describe an alternative route of adaptation through a direct role for cellular signaling components in governing gene expression via RNA interference-mediated small RNA production. Calcium-calcineurin signaling is a highly conserved signaling cascade that plays central roles in stress adaptation and virulence of eukaryotic pathogens, including the human fungal pathogen Cryptococcus neoformans. Upon activation in C. neoformans, calcineurin localizes to P-bodies, membrane-less organelles that are also the site for RNA processing. Here, we studied the role of calcineurin and its substrates in RNAi-mediated transgene silencing. Our results reveal that calcineurin regulates both the onset and the reversion of transgene silencing. We found that some calcineurin substrates that localize to P-bodies also regulate transgene silencing but in opposing directions. Small RNA sequencing in mutants lacking calcineurin or its targets revealed a role for calcineurin in small RNA production. Interestingly, the impact of calcineurin and its substrates was found to be different in genome-wide analysis, suggesting that calcineurin may regulate small RNA production in C. neoformans through additional pathways. Overall, these findings define a mechanism by which signaling machinery induced by external stimuli can directly alter gene expression to accelerate adaptative responses and contribute to genome defense.

18.
Exp Cell Res ; 434(2): 113891, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-38104645

RESUMO

MicroRNAs (miRNAs) have emerged as pivotal regulators of gene expression, playing essential roles in diverse cellular processes, including the development and progression of cancer. Among the numerous proteins influenced by miRNAs, the MARCKS/MARCKSL1 protein, a key regulator of cellular cytoskeletal dynamics and membrane-cytosol communication, has garnered significant attention due to its multifaceted involvement in various cancer-related processes, including cell migration, invasion, metastasis, and drug resistance. Motivated by the encouraging early clinical success of peptides targeting MARCKS in several pathological conditions, this review article delves into the intricate interplay between miRNAs and the MARCKS protein in cancer. Herein, we have highlighted the latest findings on specific miRNAs that modulate MARCKS/MARCKSL1 expression, providing a comprehensive overview of their roles in different cancer types. We have underscored the need for in-depth investigations into the therapeutic feasibility of targeting the miRNA-MARCKS axis in cancer, taking cues from the successes witnessed in related fields. Unlocking the full potential of miRNA-mediated MARCKS regulation could pave the way for innovative and effective therapeutic interventions against various cancer types.


Assuntos
MicroRNAs , Neoplasias , Humanos , Substrato Quinase C Rico em Alanina Miristoilada/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína Quinase C/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias/genética , Fosforilação , Proteínas de Ligação a Calmodulina/metabolismo , Proteínas dos Microfilamentos/metabolismo
19.
bioRxiv ; 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38076943

RESUMO

Phagosome maturation arrest (PMA) imposed by Mycobacterium tuberculosis ( Mtb ) is a classic tool that helps Mtb evade macrophage anti-bacterial responses. The exclusion of RAB7, a small GTPase, from Mtb -phagosomes underscores PMA. Here we report an unexpected mechanism that triggers crosstalk between the mitochondrial quality control (MQC) and the phagosome maturation pathways that reverses the PMA. CRISPR-mediated p62/SQSTM1 depletion ( p62 KD ) blocks mitophagy flux without impacting mitochondrial quality. In p62 KD cells, Mtb growth and survival are diminished, mainly through witnessing an increasingly oxidative environment and increased lysosomal targeting. The lysosomal targeting of Mtb is facilitated by enhanced TOM20 + mitochondria-derived vesicles (MDVs) biogenesis, a key MQC mechanism. In p62 KD cells, TOM20 + -MDVs biogenesis is MIRO1/MIRO2-dependent and delivered to lysosomes for degradation in a RAB7-dependent manner. Upon infection in p62 KD cells, TOM20 + -MDVs get extensively targeted to Mtb -phagosomes, inadvertently facilitating RAB7 recruitment, PMA reversal and lysosomal targeting of Mtb . Triggering MQC collapse in p62 KD cells further diminishes Mtb survival signifying cooperation between redox- and lysosome-mediated mechanisms. The MQC-anti-bacterial pathway crosstalk could be exploited for host-directed anti-tuberculosis therapies.

20.
Cureus ; 15(11): c143, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38024032

RESUMO

[This corrects the article DOI: 10.7759/cureus.43907.].

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