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1.
Curr Top Med Chem ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38847164

ABSTRACT

Alzheimer's Disease (AD) is a serious neurological illness that causes memory loss gradually by destroying brain cells. This deadly brain illness primarily strikes the elderly, impairing their cognitive and bodily abilities until brain shrinkage occurs. Modern techniques are required for an accurate diagnosis of AD. Machine learning has gained attraction in the medical field as a means of determining a person's risk of developing AD in its early stages. One of the most advanced soft computing neural network-based Deep Learning (DL) methodologies has garnered significant interest among researchers in automating early-stage AD diagnosis. Hence, a comprehensive review is necessary to gain insights into DL techniques for the advancement of more effective methods for diagnosing AD. This review explores multiple biomarkers associated with Alzheimer's Disease (AD) and various DL methodologies, including Deep Neural Networks (DNN), Convolutional Neural Networks (CNN), Recurrent Neural Networks (RNN), The k-nearest-neighbor (k-NN), Deep Boltzmann Machines (DBM), and Deep Belief Networks (DBN), which have been employed for automating the early diagnosis of AD. Moreover, the unique contributions of this review include the classification of ATN biomarkers for Alzheimer's Disease (AD), systemic description of diverse DL algorithms for early AD assessment, along with a discussion of widely utilized online datasets such as ADNI, OASIS, etc. Additionally, this review provides perspectives on future trends derived from critical evaluation of each variant of DL techniques across different modalities, dataset sources, AUC values, and accuracies.

2.
NPJ Precis Oncol ; 8(1): 130, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851780

ABSTRACT

Oral squamous cell carcinoma (OSCC) biomarker studies rarely employ multi-omic biomarker strategies and pertinent clinicopathologic characteristics to predict mortality. In this study we determine for the first time a combined epigenetic, gene expression, and histology signature that differentiates between patients with different tobacco use history (heavy tobacco use with ≥10 pack years vs. no tobacco use). Using The Cancer Genome Atlas (TCGA) cohort (n = 257) and an internal cohort (n = 40), we identify 3 epigenetic markers (GPR15, GNG12, GDNF) and 13 expression markers (IGHA2, SCG5, RPL3L, NTRK1, CD96, BMP6, TFPI2, EFEMP2, RYR3, DMTN, GPD2, BAALC, and FMO3), which are dysregulated in OSCC patients who were never smokers vs. those who have a ≥ 10 pack year history. While mortality risk prediction based on smoking status and clinicopathologic covariates alone is inaccurate (c-statistic = 0.57), the combined epigenetic/expression and histologic signature has a c-statistic = 0.9409 in predicting 5-year mortality in OSCC patients.

3.
Article in English | MEDLINE | ID: mdl-38856850

ABSTRACT

This research paper aims to explore the effect of graphite, wollastonite, and titanium dioxide as reinforcing fillers on starch-based biodegradable plastic (SBP) films. GF-SBP (graphite filler containing SBP), WF-SBP (wollastonite containing SBP), and TF-SBP (titanium dioxide containing SBP) films were developed and analyzed for various properties such as thickness, density, tensile strength, elongation break, morphology, thermal stability, solubility, moisture content, moisture absorbance, biodegradability, and antibacterial activity. The results reveal that WF-SBP films had the highest tensile strength of 5.43 MPa and greatest elongation break value of 22% as compared to other films. Thermogravimetric analysis showed that SBP films with and without filler degraded slowly between 150 and 600°C. The highest thermal stability was recorded for TF-SBP films which showed stability (11% mass loss) up to 150°C. The biodegradability test conducted using soil burial method suggested that TF-SBP film degraded within 90 days, GF-SBP films degraded completely in 120 days, and WF-SBP films took more than 120 days to degrade. The synthesized SBP films were analyzed for their antibacterial potential against gram-positive and gram-negative bacteria, and results showed that WF-SBP film exhibited the best antibacterial activity by producing a large zone of inhibition against Escherichia coli.

4.
Front Microbiol ; 15: 1363879, 2024.
Article in English | MEDLINE | ID: mdl-38846574

ABSTRACT

Marine microorganisms are renowned for being a rich source of new secondary metabolites that are significant to humans. The fungi strain KHW-7 was isolated from the seawater collected from the Gulf of Khambhat, India, and identified as Curvularia verruculosa KHW-7. On a next-generation sequencing platform, C. verruculosa KHW-7's whole-genome sequencing (WGS) and gene annotation were carried out using several bioinformatic methods. The 31.59 MB genome size, 52.3% GC, and 158 bp mean read length were discovered using WGS. This genome also contained 9,745 protein-coding genes, including 852 secreted proteins and 2048 transmembrane proteins. The antiSMASH algorithm used to analyze genomes found 25 secondary metabolite biosynthetic gene clusters (BGCs) that are abundant in terpene, non-ribosomal peptide synthetase (NRPS), and polyketides type 1 (T1PKS). To our knowledge, this is the first whole-genome sequence report of C. verruculosa. The WGS analysis of C. verruculosa KHW-7 indicated that this marine-derived fungus could be an efficient generator of bioactive secondary metabolites and an important industrial enzyme, both of which demand further investigation and development.

5.
Water Environ Res ; 96(5): e11033, 2024.
Article in English | MEDLINE | ID: mdl-38720414

ABSTRACT

The escalating issue of microplastic (MP) pollution poses a significant threat to the marine environment due to increasing plastic production and improper waste management. The current investigation was aimed at quantifying the MP concentration on 25 beaches on the Maharashtra coast, India. Beach sediments (1 kg) were collected from each site, with five replicates to evaluate the extent of MPs. The samples were homogenized, and three 20 g replicas were prepared for subsequent analysis. Later, the samples were sieved, and MPs were extracted using previously published protocols. The abundance of MPs found as 1.56 ± 0.79 MPs/g, ranges from 0.43 ± 0.07 to 3 ± 0.37 MPs/g. Fibers were found as the most abundant shape of MPs. Size-wise classification revealed dominance of <1 mm and 1-2 mm-sized MPs. Blue- and black-colored MPs were recorded dominantly. Polymer identification of MPs revealed polyurethane, polypropylene, polyvinyl chloride, acrylic or polymethyl methacrylate, and rubber. The findings revealed that MPs were found to be higher at highly impacted sites, followed by moderately impacted sites and low-impacted sites, possibly due to a different degree of anthropogenic pressure. The study recommended the urgent need for effective policy to prevent plastics accumulation in the coastal environment of Maharashtra State, India. PRACTITIONER POINTS: The study investigated the abundance and distribution of microplastics in the marine environment, specifically in sediments. The most common type of microplastic found was fibers, followed by fragments and films. Microplastics were found to pose a potential risk to the marine ecosystem, although further research is needed to fully understand their ecological impact. Future research should focus on expanding the sample size, assessing long-term effects, exploring sources and pathways, and considering size and shape of microplastics. The findings recommended urgent action to mitigate plastic pollution in Maharashtra coast.


Subject(s)
Bathing Beaches , Environmental Monitoring , Geologic Sediments , Microplastics , India , Microplastics/analysis , Geologic Sediments/chemistry , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/chemistry , Plastics/chemistry , Plastics/analysis
6.
PeerJ ; 12: e17328, 2024.
Article in English | MEDLINE | ID: mdl-38770094

ABSTRACT

Nanotechnology and nanoparticles have gained massive attention in the scientific community in recent years due to their valuable properties. Among various AgNPs synthesis methods, microbial approaches offer distinct advantages in terms of cost-effectiveness, biocompatibility, and eco-friendliness. In the present research work, investigators have synthesized three different types of silver nanoparticles (AgNPs), namely AgNPs-K, AgNPs-M, and AgNPs-E, by using Klebsiella pneumoniae (MBC34), Micrococcus luteus (MBC23), and Enterobacter aerogenes (MBX6), respectively. The morphological, chemical, and elemental features of the synthesized AgNPs were analyzed by using UV-Vis spectroscopy (UV-Vis), Fourier transform-infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscope (FESEM) and energy-dispersive spectroscopy (EDX). UV-Vis absorbance peaks were obtained at 475, 428, and 503 nm for AgNPs-K, AgNPs-M, and AgNPs-E, respectively. The XRD analysis confirmed the crystalline nature of the synthesized AgNPs, having peaks at 26.2°, 32.1°, and 47.2°. At the same time, the FTIR showed bands at 599, 963, 1,693, 2,299, 2,891, and 3,780 cm-1 for all the types of AgNPs indicating the presence of bacterial biomolecules with the developed AgNPs. The size and morphology of the AgNPs varied from 10 nm to several microns and exhibited spherical to porous sheets-like structures. The percentage of Ag varied from 37.8% (wt.%) to 61.6%, i.e., highest in AgNPs-K and lowest in AgNPs-M. Furthermore, the synthesized AgNPs exhibited potential for environmental remediation, with AgNPs-M exhibiting the highest removal efficiency (19.24% at 120 min) for methyl orange dye in simulated wastewater. Further, all three types of AgNPs were evaluated for the removal of methyl orange dye from the simulated wastewater, where the highest dye removal percentage was 19.24% at 120 min by AgNPs-M. Antibacterial potential of the synthesized AgNPs assessment against both Gram-positive (GPB) Bacillus subtilis (MBC23), B. cereus (MBC24), and Gram-negative bacteria Enterococcus faecalis (MBP13) revealed promising results, with AgNPs-M, exhibiting the largest zone of inhibition (12 mm) against GPB B. megaterium. Such investigation exhibits the potential of the bacteria for the synthesis of AgNPs with diverse morphology and potential applications in environmental remediation and antibacterial therapy-based synthesis of AgNPs.


Subject(s)
Azo Compounds , Metal Nanoparticles , Micrococcus luteus , Silver , Silver/chemistry , Silver/pharmacology , Silver/metabolism , Metal Nanoparticles/chemistry , Azo Compounds/chemistry , Azo Compounds/pharmacology , Azo Compounds/metabolism , Micrococcus luteus/drug effects , Spectroscopy, Fourier Transform Infrared , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/metabolism , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Enterobacter aerogenes/drug effects , Enterobacter aerogenes/metabolism , X-Ray Diffraction , Water Pollutants, Chemical/metabolism , Coloring Agents/chemistry , Coloring Agents/pharmacology
7.
JAMA Netw Open ; 7(5): e248881, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38700865

ABSTRACT

Importance: With increased use of robots, there is an inadequate understanding of minimally invasive modalities' time costs. This study evaluates the operative durations of robotic-assisted vs video-assisted lung lobectomies. Objective: To compare resource utilization, specifically operative time, between video-assisted and robotic-assisted thoracoscopic lung lobectomies. Design, Setting, and Participants: This retrospective cohort study evaluated patients aged 18 to 90 years who underwent minimally invasive (robotic-assisted or video-assisted) lung lobectomy from January 1, 2020, to December 31, 2022, with 90 days' follow-up after surgery. The study included multicenter electronic health record data from 21 hospitals within an integrated health care system in Northern California. Thoracic surgery was regionalized to 4 centers with 14 board-certified general thoracic surgeons. Exposures: Robotic-assisted or video-assisted lung lobectomy. Main Outcomes and Measures: The primary outcome was operative duration (cut to close) in minutes. Secondary outcomes were length of stay, 30-day readmission, and 90-day mortality. Comparisons between video-assisted and robotic-assisted lobectomies were generated using the Wilcoxon rank sum test for continuous variables and the χ2 test for categorical variables. The average treatment effects were estimated with augmented inverse probability treatment weighting (AIPTW). Patient and surgeon covariates were adjusted for and included patient demographics, comorbidities, and case complexity (age, sex, race and ethnicity, neighborhood deprivation index, body mass index, Charlson Comorbidity Index score, nonelective hospitalizations, emergency department visits, a validated laboratory derangement score, a validated institutional comorbidity score, a surgeon-designated complexity indicator, and a procedural code count), and a primary surgeon-specific indicator. Results: The study included 1088 patients (median age, 70.1 years [IQR, 63.3-75.8 years]; 704 [64.7%] female), of whom 446 (41.0%) underwent robotic-assisted and 642 (59.0%) underwent video-assisted lobectomy. The median unadjusted operative duration was 172.0 minutes (IQR, 128.0-226.0 minutes). After AIPTW, there was less than a 10% difference in all covariates between groups, and operative duration was a median 20.6 minutes (95% CI, 12.9-28.2 minutes; P < .001) longer for robotic-assisted compared with video-assisted lobectomies. There was no difference in adjusted secondary patient outcomes, specifically for length of stay (0.3 days; 95% CI, -0.3 to 0.8 days; P = .11) or risk of 30-day readmission (adjusted odds ratio, 1.29; 95% CI, 0.84-1.98; P = .13). The unadjusted 90-day mortality rate (1.3% [n = 14]) was too low for the AIPTW modeling process. Conclusions and Relevance: In this cohort study, there was no difference in patient outcomes between modalities, but operative duration was longer in robotic-assisted compared with video-assisted lung lobectomy. Given that this elevated operative duration is additive when applied systematically, increased consideration of appropriate patient selection for robotic-assisted lung lobectomy is needed to improve resource utilization.


Subject(s)
Pneumonectomy , Robotic Surgical Procedures , Thoracic Surgery, Video-Assisted , Humans , Female , Male , Middle Aged , Robotic Surgical Procedures/statistics & numerical data , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/economics , Aged , Retrospective Studies , Pneumonectomy/methods , Pneumonectomy/statistics & numerical data , Thoracic Surgery, Video-Assisted/methods , Thoracic Surgery, Video-Assisted/statistics & numerical data , Adult , Operative Time , Operating Rooms/statistics & numerical data , Aged, 80 and over , Length of Stay/statistics & numerical data , Lung Neoplasms/surgery , Adolescent , Treatment Outcome
8.
Article in English | MEDLINE | ID: mdl-38706351

ABSTRACT

BACKGROUND: Interaction of PD-1 protein (present on immune T-cell) with its ligand PD-L1 (over-expressed on cancerous cell) makes the cancerous cell survive and thrive. The association of PD-1/PD-L1 represents a classical protein-protein interaction (PPI), where receptor and ligand binding through a large flat surface. Blocking the PD-1/PDL-1 complex formation can restore the normal immune mechanism, thereby destroying cancerous cells. However, the PD-1/PDL1 interactions are only partially characterized. OBJECTIVE: We aim to comprehend the time-dependent behavior of PD-1 upon its binding with PD-L1. METHOD: The current work focuses on a molecular dynamics simulation (MDs) simulation study of apo and ligand bound PD-1. RESULTS: Our simulation reveals the flexible nature of the PD-1, both in apo and bound form. Moreover, the current study also differentiates the type of strong and weak interactions which could be targeted to overcome the complex formation. CONCLUSION: The current article could provide a valuable structural insight about the target protein (PD-1) and its ligand (PD-L1) which could open new opportunities in developing small molecule inhibitors (SMIs) targeting either PD-1 or PD-L1.

9.
Water Environ Res ; 96(5): e11029, 2024 May.
Article in English | MEDLINE | ID: mdl-38708452

ABSTRACT

Microplastics (MPs) pollution has wreaked havoc on biodiversity and food safety globally. The false ingestion of MPs causes harmful effects on organisms, resulting in a decline in biodiversity. The present review comprehended the current knowledge of MP contamination in Crustacea and Mollusca from 75 peer-reviewed articles published in Asia between 2015 and 2023. A total of 79 species (27 Crustacea and 52 Mollusca) have been recorded to be contaminated with MPs. Out of the total 27 species of Crustacea, Metopograpsus quadridentatus (327.56 MPs/individual) and Balanus albicostatus (0.42 MPs/individual) showed the highest and lowest contamination, respectively. Out of the total 52 species of Mollusca, Dolabella auricularia (2325 MPs/individual) and Crassostrea gigas and Mytilus edulis (0.2 MPs/individual) showed the highest and lowest contamination, respectively. In terms of country-wise MP contamination, China has the highest number of contaminated species in both phylums among Asia. Findings of pollution indices revealed a very high risk of MP contamination in all the countries. Fiber was reported predominantly in both groups. Blue and black-colored MPs having <500 µm and <500 µm-1 mm size were found dominantly in Crustacea and Mollusca, respectively. Polypropylene was recorded as the dominant plastic polymer in both Crustacea and Mollusca. In essence, this review has provided a comprehensive insight into MP concentration in Crustacea and Mollusca of Asia, highlighting variations among species and geographic locations. This understanding is crucial for tackling urgent environmental challenges, safeguarding human health, and promoting global sustainability initiatives amid the escalating issue of plastic pollution. PRACTITIONER POINTS: Microplastic pollution has created havoc on biodiversity and food safety. A total of 27 and 52 species of crustaceans and Mollusca have been recorded to be contaminated with MPs. Metopograpsus quadridentate and Dolabella auricularia have shown higher MPs contamination. Polypropylene was recorded as the dominant plastic polymer in both crustacean and Mollusca. Findings of pollution indices revealed a very high risk of MP contamination in all the countries.


Subject(s)
Crustacea , Microplastics , Mollusca , Water Pollutants, Chemical , Animals , Water Pollutants, Chemical/analysis , Risk Assessment , Asia , Microplastics/analysis , Environmental Monitoring
10.
Front Chem ; 12: 1389846, 2024.
Article in English | MEDLINE | ID: mdl-38746020

ABSTRACT

This study investigated the synthesis of bioactive peptides from sheep milk through fermentation with Limosilactobacillus fermentum KGL4 MTCC 25515 strain and assessed lipase inhibition, ACE inhibition, α-glucosidase inhibition, and α-amylase inhibition activities during the fermentation process. The study observed the highest activities, reaching 74.82%, 70.02%, 72.19%, and 67.08% (lipase inhibition, ACE inhibition, α-glucosidase inhibition, and α-amylase inhibition) after 48 h at 37°C, respectively. Growth optimization experiments revealed that a 2.5% inoculation rate after 48 h of fermentation time resulted in the highest proteolytic activity at 9.88 mg/mL. Additionally, fractions with less than 3 kDa of molecular weight exhibited superior ACE-inhibition and anti-diabetic activities compared to other fractions. Fermentation of sheep milk with KGL4 led to a significant reduction in the excessive production of NO, TNF-α, IL-6, and IL-1ß produced in RAW 267.4 cells upon treatment with LPS. Peptides were purified utilizing SDS-PAGE and electrophoresis on 2D gels, identifying a maximum number of proteins bands ranging 10-70 kDa. Peptide sequences were cross-referenced with AHTPDB and BIOPEP databases, confirming potential antihypertensive and antidiabetic properties. Notably, the peptide (GPFPILV) exhibited the highest HPEPDOCK score against both α-amylase and ACE.

11.
JPGN Rep ; 5(2): 197-199, 2024 May.
Article in English | MEDLINE | ID: mdl-38756133

ABSTRACT

Approved options for advanced therapy in pediatric inflammatory bowel disease (IBD) are limited. Although Janus kinase (JAK) inhibitors are approved in adult IBD, their benefit in pediatric populations is not yet delineated. We present a 13-year-old female patient with ulcerative colitis (UC) refractory to numerous therapies and courses of prednisone that ultimately responded to a JAK inhibitor. Initial treatment consisted of 5-aminosalicylate and azathioprine. This was changed to adalimumab due to persistent symptoms. Repeat colonoscopy revealed pancolitis, thus she was transitioned to vedolizumab. She was hospitalized twice for uncontrolled symptoms on vedolizumab and subsequent scope showed continued pancolitis. As a result, she transitioned to ustekinumab without symptomatic relief after adjusting to monthly dosing. The family declined colectomy, opting to exhaust all medical therapies. Upadacitinib was started and her symptoms resolved within 1 week, and she remains in steroid-free remission. This case illustrates the possible role of JAK inhibitors in extensively refractory pediatric UC patients before colectomy.

12.
Ann Appl Stat ; 18(2)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38737575

ABSTRACT

Mendelian randomization (MR) is a widely-used method to estimate the causal relationship between a risk factor and disease. A fundamental part of any MR analysis is to choose appropriate genetic variants as instrumental variables. Genome-wide association studies often reveal that hundreds of genetic variants may be robustly associated with a risk factor, but in some situations investigators may have greater confidence in the instrument validity of only a smaller subset of variants. Nevertheless, the use of additional instruments may be optimal from the perspective of mean squared error even if they are slightly invalid; a small bias in estimation may be a price worth paying for a larger reduction in variance. For this purpose, we consider a method for "focused" instrument selection whereby genetic variants are selected to minimise the estimated asymptotic mean squared error of causal effect estimates. In a setting of many weak and locally invalid instruments, we propose a novel strategy to construct confidence intervals for post-selection focused estimators that guards against the worst case loss in asymptotic coverage. In empirical applications to: (i) validate lipid drug targets; and (ii) investigate vitamin D effects on a wide range of outcomes, our findings suggest that the optimal selection of instruments does not involve only a small number of biologically-justified instruments, but also many potentially invalid instruments.

13.
Cell Biochem Funct ; 42(3): e4022, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38655589

ABSTRACT

Over the years, the administration of antibiotics for the purpose of addressing bacterial infections has become increasingly challenging due to the increased prevalence of antimicrobial resistance exhibited by various strains of bacteria. Multidrug-resistant (MDR) bacterial species are rising due to the unavailability of novel antibiotics, leading to higher mortality rates. With these conditions, there is a need for alternatives in which phage therapy has made promising results. Phage-derived endolysins, phage cocktails, and bioengineered phages are effective and have antimicrobial properties against MDR and extensively drug-resistant strains. Despite these, it has been observed that phages can give antimicrobial activity to more than one bacterial species. Thus, phage cocktail against resistant strains provides broad spectrum treatment and magnitude of effectivity, which is many folds higher than antibiotics. Many commercially available endolysins such as Staphefekt SA.100, Exebacase (CF-301), and N-Rephasin®SAL200 are used in biofilm penetration and treating plant diseases. The role of CMP1 phage endolysin in transgenic tomato plants in preventing Clavibacter michiganensis infection and the effectiveness of phage in protecting Atlantic salmon from vibriosis have been reported. Furthermore, phage-derived endolysin therapy, such as TSPphg phage exogenous treatment, can aid in disrupting cell walls, leading to bacterial cell lysis. As animals in aquaculture and slaughterhouses are highly susceptible to bacterial infections, effective phage therapy instead of antibiotics can help treat poultry animals, preserve them, and facilitate disease-free trade. Using bioengineered phages and phage cocktails enhances the effectiveness by providing a broad spectrum of phages and target specificity. Research is currently being conducted on clinical trials to confirm the efficacy of engineered phages and phage cocktails in humans. Although obtaining commercial approval may be time-consuming, it will be beneficial in the postantibiotic era. This review provides an overview of the significance of phage therapy as a potential alternative to antibiotics in combating resistant bacterial strains and its application to various fields and emphasizes the importance of safeguarding and ensuring treatment efficacy.


Subject(s)
Anti-Bacterial Agents , Bacteriophages , Endopeptidases , Phage Therapy , Anti-Bacterial Agents/pharmacology , Humans , Animals , Bacterial Infections/therapy , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Bacteria/drug effects , Bacteria/virology
14.
ADMET DMPK ; 12(1): 63-105, 2024.
Article in English | MEDLINE | ID: mdl-38560713

ABSTRACT

Background and Purpose: The blood-brain barrier (BBB), a critical interface of specialized endothelial cells, plays a pivotal role in regulating molecular and ion transport between the central nervous system (CNS) and systemic circulation. Experimental Approach: This review aims to delve into the intricate architecture and functions of the BBB while addressing challenges associated with delivering therapeutics to the brain. Historical milestones and contemporary insights underscore the BBB's significance in protecting the CNS. Key Results: Innovative approaches for enhanced drug transport include intranasal delivery exploiting olfactory and trigeminal pathways, as well as techniques like temporary BBB opening through chemicals, receptors, or focused ultrasound. These avenues hold the potential to reshape conventional drug delivery paradigms and address the limitations posed by the BBB's selectivity. Conclusion: This review underscores the vital role of the BBB in maintaining CNS health and emphasizes the importance of effective drug delivery through this barrier. Nanoparticles emerge as promising candidates to overcome BBB limitations and potentially revolutionize the treatment of CNS disorders. As research progresses, the application of nanomaterials shows immense potential for advancing neurological therapeutics, albeit with careful consideration of safety aspects.

15.
Chem Biodivers ; : e202301903, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38623839

ABSTRACT

Breast cancer is a global health concern, demanding innovative treatments. Targeting the Transforming Growth Factor-beta (TGF-ß) signaling pathway, pivotal in breast cancer, is a promising approach. TGF-ß inhibits proliferation via G1 phase cell cycle arrest, acting as a suppressor initially, but in later stages, it promotes progression by enhancing motility, invasiveness, and metastasis formation. This study explores naturally occurring flavonoids' interactions with TGF-ß. Using molecular docking against the protein's crystal structure (PDB Id: 1PY5), Gossypin showed the highest docking score and underwent molecular dynamics simulation, revealing complex flexibility and explaining how flavonoids impede TGF-ß signaling in breast cancer. ADMET predictions adhered to Lipinski's rule of Five. Insights into flavonoid-TGF-ß binding offer a novel angle for breast cancer treatment. Flavonoids having a good docking score like gossypin, morin, luteolin and taxifolin shown potent cytotoxic effect on breast cancer cell line, MCF-7. Understanding these interactions could inspire flavonoid-based therapies targeting TGF-ß to halt breast cancer growth. These findings pave the way for personalized, targeted breast cancer therapies, offering hope against this formidable disease.

17.
Surg Open Sci ; 19: 118-124, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38655068

ABSTRACT

Background: Disparities exist throughout surgery. We aimed to assess for racial/ethnic disparities among outcomes in a large thoracic surgery patient population. Methods: We reviewed all thoracic surgery patients treated at our integrated health system from January 1, 2016-December 31, 2020. Post-operative outcomes including length of stay (LOS), 30-day return to the emergency department (30d-ED), 30-day readmission, 30- and 90-day outpatient appointments, and 30- and 90-day mortality were compared by race/ethnicity. Bivariate analyses and multivariable logistic regression were performed. Our multivariable models adjusted for age, sex, body mass index, Charlson Comorbidity Index, surgery type, neighborhood deprivation index, insurance, and home region. Results: Of 2730 included patients, 59.4 % were non-Hispanic White, 15.0 % were Asian, 11.9 % were Hispanic, 9.6 % were Black, and 4.1 % were Other. Median (Q1-Q3) LOS (in hours) was shortest among non-Hispanic White (37.3 (29.2-76.1)) and Other (36.5 (29.3-75.4)) patients followed by Hispanic (46.8 (29.9-78.1)) patients with Asian (51.3 (30.7-81.9)) and Black (53.7 (30.6-101.6)) patients experiencing the longest LOS (p < 0.01). 30d-ED rates were highest among Hispanic patients (21.3 %), followed by Black (19.2 %), non-Hispanic White (18.1 %), Asian (13.4 %), and Other (8.0 %) patients (p < 0.01). On multivariable analysis, Hispanic ethnicity (Odds Ratio (OR) 1.43 (95 % CI 1.03-1.97)) and Medicaid insurance (OR 2.37 (95 % CI 1.48-3.81)) were associated with higher 30d-ED rates. No racial/ethnic disparities were found among other outcomes. Conclusions: Despite parity across multiple surgical outcomes, disparities remain related to patient encounters within our system. Health systems must track such disparities in addition to standard clinical outcomes. Key message: While our large integrated health system has been able to demonstrate parity across many major surgical outcomes among our thoracic surgery patients, race/ethnicity disparities persist including in the number of post-operative return trips to the emergency department. Tracking outcome disparities to a granular level such as return visits to the emergency department and number of follow up appointments is critical as health systems strive to achieve equitable care.

18.
Front Microbiol ; 15: 1355750, 2024.
Article in English | MEDLINE | ID: mdl-38468848

ABSTRACT

Numerous bacterial species associate with plants through commensal, mutualistic, or parasitic association, affecting host physiology and health. The mechanism for such association is intricate and involves the secretion of multiple biochemical substances through dedicated protein systems called secretion systems SS. Eleven SS pathways deliver protein factors and enzymes in their immediate environment or host cells, as well as in competing microbial cells in a contact-dependent or independent fashion. These SS are instrumental in competition, initiation of infection, colonization, and establishment of association (positive or negative) with host organisms. The role of SS in infection and pathogenesis has been demonstrated for several phytopathogens, including Agrobacterium, Xanthomonas, Ralstonia, and Pseudomonas. Since there is overlap in mechanisms of establishing association with host plants, several studies have investigated the role of SSs in the interaction of plant and beneficial bacteria, including symbiotic rhizobia and plant growth bacteria (PGPB). Therefore, the present review updates the role of different SSs required for the colonization of beneficial bacteria such as rhizobia, Burkholderia, Pseudomonas, Herbaspirillum, etc., on or inside plants, which can lead to a long-term association. Most SS like T3SS, T4SS, T5SS, and T6SS are required for the antagonistic activity needed to prevent competing microbes, including phytopathogens, ameliorate biotic stress in plants, and produce substances for successful colonization. Others are required for chemotaxis, adherence, niche formation, and suppression of immune response to establish mutualistic association with host plants.

19.
Front Microbiol ; 15: 1326390, 2024.
Article in English | MEDLINE | ID: mdl-38533327

ABSTRACT

The growth of crop plants, particularly spinach (Spinacia oleracea L.), can be significantly impeded by salinity and drought. However, pre-treating spinach plants with traditional biofertilizers like Jeevamrit and Beejamrit (JB) substantially reverses the salinity and drought-induced inhibitory effects. Hence, this study aims to elucidate the underlying mechanisms that govern the efficacy of traditional fertilizers. The present work employed comprehensive biochemical, physiological, and molecular approaches to investigate the processes by which JB alleviates abiotic stress. The JB treatment effectively boosts spinach growth by increasing nutrient uptake and antioxidant enzyme activity, which mitigates the detrimental effects of drought and salinity-induced stress. Under salt and drought stress conditions, the application of JB resulted in an impressive rise in germination percentages of 80 and 60%, respectively. In addition, the application of JB treatment resulted in a 50% decrease in electrolyte leakage and a 75% rise in the relative water content of the spinach plants. Furthermore, the significant reduction in proline and glycine betaine levels in plants treated with JB provides additional evidence of the treatment's ability to prevent cell death caused by environmental stressors. Following JB treatment, the spinach plants exhibited substantially higher total chlorophyll content was also observed. Additionally, using 16S rRNA sequencing, we discovered and characterized five plant-beneficial bacteria from the JB bio-inoculants. These bacterial isolates comprise a number of traits that contribute to growth augmentation in plants. These evidences suggest that the presence of the aforesaid microorganisms (along with additional ones) is accountable for the JB-mediated stimulation of plant growth and development.

20.
PeerJ ; 12: e17065, 2024.
Article in English | MEDLINE | ID: mdl-38495759

ABSTRACT

Background: The present study investigated the population structure and breeding biology of the burrowing brachyuran crab species Dotilla blanfordi Alcock, 1900, which is commonly found on the sandy beach of Bhavnagar, located on the Gulf of Kachchh, Gujarat coast, India. Methods: Monthly sampling was conducted from February 2021 to January 2022 at the time of low tide using three line transects perpendicular to the water line, intercepted by a quadrate (0.25 m2) each at three different levels of the middle intertidal region: 20 m, 70 m, and 120 m. The quadrate area was excavated up to 30 cm and sieved for specimen collection. The collected specimens were categorised into different sexes viz., male, non-ovigerous female, or ovigerous female. For the fecundity study of D. blanfordi, the carapace width (mm) as a measure of size as well as their wet weight (g), size, number, and mass of their eggs were also recorded. Results: The study revealed sexual dimorphism among the population, with females having significantly smaller sizes as compared to males. The overall population was skewed towards females, with a bimodal distribution of males and females. The occurrence of ovigerous females throughout the year suggests that the population breeds incessantly throughout the year, with the highest occurrence in August and September. A positive correlation was observed between the morphology of crabs (carapace width and wet body weight) and the size, number, and mass of eggs.


Subject(s)
Brachyura , Animals , Female , Male , Brachyura/anatomy & histology , Fertility , Sex Characteristics , India , Biology
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