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1.
Science ; 384(6701): 1227-1235, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38870286

ABSTRACT

We present a design strategy for fabricating ultrastable phase-pure films of formamidinium lead iodide (FAPbI3) by lattice templating using specific two-dimensional (2D) perovskites with FA as the cage cation. When a pure FAPbI3 precursor solution is brought in contact with the 2D perovskite, the black phase forms preferentially at 100°C, much lower than the standard FAPbI3 annealing temperature of 150°C. X-ray diffraction and optical spectroscopy suggest that the resulting FAPbI3 film compresses slightly to acquire the (011) interplanar distances of the 2D perovskite seed. The 2D-templated bulk FAPbI3 films exhibited an efficiency of 24.1% in a p-i-n architecture with 0.5-square centimeter active area and an exceptional durability, retaining 97% of their initial efficiency after 1000 hours under 85°C and maximum power point tracking.

2.
Front Microbiol ; 15: 1406904, 2024.
Article in English | MEDLINE | ID: mdl-38939182

ABSTRACT

This review aims to comprehensively chronicle the biosynthesis, classification, properties, and applications of bacteriocins produced by Weissella genus strains, particularly emphasizing their potential benefits in food preservation, human health, and animal productivity. Lactic Acid Bacteria (LAB) are a class of microorganisms well-known for their beneficial role in food fermentation, probiotics, and human health. A notable property of LAB is that they can synthesize antimicrobial peptides known as bacteriocins that exhibit antimicrobial action against both closely related and other bacteria as well. Bacteriocins produced by Weissella spp. are known to exhibit antimicrobial activity against several pathogenic bacteria including food spoilage species, making them highly invaluable for potential application in food preservation and food safety. Importantly, they provide significant health benefits to humans, including combating infections, reducing inflammation, and modulating the gut microbiota. In addition to their applications in food fermentation and probiotics, Weissella bacteriocins show promising prospects in poultry production, processing, and improving animal productivity. Future research should explore the utilization of Weissella bacteriocins in innovative food safety measures and medical applications, emphasizing their potential to combat antibiotic-resistant pathogens, enhance gut microbiota composition and function, and synergize with existing antimicrobial therapies.

3.
Homeopathy ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714214

ABSTRACT

BACKGROUND: Prior vaccination is often studied for its impact on individuals' post-infection prognosis. Ayurveda, Yoga, Unani, Siddha and Homeopathy (AYUSH) medicines, advised by the Government of India as prophylaxis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic, were consumed by the masses in 2020. A study was therefore undertaken to observe any association between the prior usage of AYUSH prophylactic medicines and post-infection severity as reported by recovered COVID-19 individuals. METHODS: This was a retrospective, multi-centre, cohort study conducted in 21 cities of India from 5th August to 30th November 2020. Data from recovered COVID-19 patients, of either sex or any age, captured information about AYUSH prophylactic medicines intake prior to infection, disease severity, symptomatology, duration of complaints, etc. The study participants were grouped into AYUSH intake and non-intake. Primary composite outcome was the disease clinical course. Secondary clinical outcomes were the rate of and time to clinical recovery. RESULTS: Data of 5,023 persons were analysed. Ayurveda or homeopathic prophylactic medicines were consumed by more than half of the study participants: that is, 56.85% (n = 1,556) and 56.81% (n = 1,555) respectively. The overall adjusted protective effect (PE) of AYUSH prophylactic intake against moderate/severe forms of COVID-19 disease was 56.7% (95% confidence interval [CI], 48.7 to 63.50; p < 0.001). Adjusted PE for homeopathy and Siddha was 52.9% (95% CI, 42.30 to 61.50; p < 0.001) and 59.8% (95% CI, 37.80 to 74.10; p < 0.001), respectively. A statistically significant association was found between AYUSH prophylactic medicine intake and clinical recovery more frequently by the 3rd day of illness (χ2 = 9.01; p = 0.002). Time to resolution of symptoms in the AYUSH intake group was on average 0.3 days earlier than in the non-intake group (p = 0.002). CONCLUSION: AYUSH prophylactics were associated with statistically significant levels of protection against COVID-19 disease severity. Amongst these, previous intake of homeopathy or Siddha medicines was associated with some protection against moderate/severe illness and with a somewhat quicker clinical recovery. Prospective studies with experimental research design are needed to validate the findings of this study. STUDY REGISTRATION: Clinical Trials Registry-India (CTRI/2020/08/027000).

4.
J Am Chem Soc ; 146(23): 16128-16147, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38815003

ABSTRACT

One of the primary methods for band gap tuning in metal halide perovskites has been halide (I/Br) mixing. Despite widespread usage of this type of chemical substitution in perovskite photovoltaics, there is still little understanding of the structural impacts of halide alloying, with the assumption being the formation of ideal solid solutions. The FASnI3-xBrx (x = 0-3) family of compounds provides the first example where the assumption breaks down, as the composition space is broken into two unique regimes (x = 0-2.9; x = 2.9-3) based on their average structure with the former having a 3D and the latter having an extended 3D (pseudo 0D) structure. Pair distribution function (PDF) analyses further suggest a dynamic 5s2 lone pair expression resulting in increasing levels of off-centering of the central Sn as the Br concentration is increased. These antiferroelectric distortions indicate that even the x = 0-2.9 phase space behaves as a nonideal solid-solution on a more local scale. Solid-state NMR confirms the difference in local structure yielding greater insight into the chemical nature and local distributions of the FA+ cation. In contrast to the FAPbI3-xBrx series, a drastic photoluminescence (PL) quenching is observed with x ≥ 1.9 compounds having no observable PL. Our detailed studies attribute this quenching to structural transitions induced by the distortions of the [SnBr6] octahedra in response to stereochemically expressed lone pairs of electrons. This is confirmed through density functional theory, having a direct impact on the electronic structure.

5.
Homeopathy ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38821071

ABSTRACT

BACKGROUND: Even though several initiatives have been undertaken in different locations worldwide to collect clinical data in homeopathy, it is important to further investigate these aspects in the context of health care in India. OBJECTIVE: The study aimed to gather and analyze patients' clinical data and to derive insights into homeopathic treatment using an internet-based software program for data storage, retrieval and repertorization. METHODS: A multi-center observational study was conducted across 14 homeopathy outpatient clinics in India that are affiliated with the Central Council for Research in Homoeopathy (CCRH). Patient symptoms and demographic details were documented anonymously, and prescriptions were guided by repertorial suggestions from the Vithoulkas Compass software. During follow-up visits, treatment outcome was also recorded using an online assessment form. A retrospective analysis of data on patients' demographics, follow-up visits, morbidity (International Classification of Diseases 11th Revision), rubrics used, prescribed medicines and the level of improvement was achieved using Microsoft Excel-generated pivot tables. RESULTS: Throughout the study duration of one year a total of 2,811 patients attended the 14 outpatient clinics, of whom 2,468 were new patients with a total of 2,172 initial homeopathic prescription entries. Across the study, there were 3,491 prescriptions and 1,628 follow-up consultations for 868 follow-up patients, all of which data were thoroughly analyzed. The highest frequency of patients was in the 20-49 age group, and a higher proportion of the patients overall was female. Musculoskeletal, dermatological and respiratory complaints were the most frequently reported. The rubrics "Desire for sweets" and "Desire for spices" emerged as the most commonly used in the repertorizations. Further, Sulphur stood out as the most commonly prescribed medicine overall. With homeopathic treatment, some degree of clinical improvement was reported in 86% of the follow-up cases. CONCLUSION: Homeopathy is prescribed in CCRH outpatient clinics for a wide range of ailments in people across India, with at least some clinical improvement noted in a high proportion of those patients. The large-scale systematic data collection in these clinics has provided clear insights into the use and clinical value of homeopathy in India, with the potential to build a substantive nationwide data inventory over time.

6.
BMC Nephrol ; 25(1): 120, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38570752

ABSTRACT

BACKGROUND: Chronic Kidney Disease of unknown cause (CKDu) a disease of exclusion, and remains unexplained in various parts of the world, including India. Previous studies have reported mixed findings about the role of heavy metals or agrochemicals in CKDu. These studies compared CKDu with healthy controls but lacked subjects with CKD as controls. The purpose of this study was to test the hypothesis whether heavy metals, i.e. Arsenic (As), Cadmium (Cd), Lead (Pb), and Chromium (Cr) are associated with CKDu, in central India. METHODS: The study was conducted in a case-control manner at a tertiary care hospital. CKDu cases (n = 60) were compared with CKD (n = 62) and healthy subjects (n = 54). Blood and urine levels of As, Cd, Pb, and Cr were measured by Inductively Coupled Plasma- Optical Emission Spectrometry. Pesticide use, painkillers, smoking, and alcohol addiction were also evaluated. The median blood and urine metal levels were compared among the groups by the Kruskal-Wallis rank sum test. RESULTS: CKDu had significantly higher pesticide and surface water usage as a source of drinking water. Blood As levels (median, IQR) were significantly higher in CKDu 91.97 (1.3-132.7) µg/L compared to CKD 4.5 (0.0-58.8) µg/L and healthy subjects 39.01 (4.8-67.4) µg/L (p < 0.001) On multinominal regression age and sex adjusted blood As was independently associated with CKDu[ OR 1.013 (95%CI 1.003-1.024) P < .05].Blood and urinary Cd, Pb, and Cr were higher in CKD compared to CKDu (p > .05). Urinary Cd, Pb and Cr were undetectable in healthy subjects and were significantly higher in CKDu and CKD compared to healthy subjects (P = < 0.001). There was a significant correlation of Cd, Pb and Cr in blood and urine with each other in CKDu and CKD subjects as compared to healthy subjects. Surface water use also associated with CKDu [OR 3.178 (95%CI 1.029-9.818) p < .05). CONCLUSION: The study showed an independent association of age and sex adjusted blood As with CKDu in this Indian cohort. Subjects with renal dysfunction (CKDu and CKD) were found to have significantly higher metal burden of Pb, Cd, As, and Cr as compared to healthy controls. CKDu subjects had significantly higher pesticide and surface water usage, which may be the source of differential As exposure in these subjects.


Subject(s)
Arsenic , Drinking Water , Metals, Heavy , Pesticides , Renal Insufficiency, Chronic , Humans , Cadmium/analysis , Case-Control Studies , Lead , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/etiology , Arsenic/analysis , Chromium
7.
Indian J Crit Care Med ; 28(4): 329-335, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38585323

ABSTRACT

Aims and background: Acute poisoning is one of the most common emergencies in India and around the world. Understanding the factors associated with mortality can aid us in devising appropriate preventive strategies to curtail deaths due to poisoning. Purpose of this study is to find various factors that determine the mortality among acute poisoning cases admitted in a tertiary care center. Materials and methods: A retrospective hospital records-based study was conducted at Chengalpattu Medical College Hospital. The study included 2,123 cases of various poisoning cases admitted for a year from January to December 2022. Cases of bites, stings, drowning, and hanging were excluded. Information on sociodemographic profile, type of poison, time since ingestion and admission, and treatment outcome were collected using a structured pro forma. Results: The mean age of the study population was 29.90 ± 14.98 years. Poisoning was found to be predominantly among males (56.42%) and residents of rural areas (58%). Insecticide consumption (27.0%) was the most common modality, followed by oleander poisoning (20%), corrosive poison (17%), rat poison (15%), tablet poison (13%), and other poisons. The overall case fatality rate (CFR) was 5.2%, with the highest CFR of 12.25% with insecticide poisoning. In multivariate analysis, Glasgow coma scale (GCS) score at admission is the only parameter showing a statistically significant association with mortality (adjusted odds-ratio 0.271(0.2-0.38, p-value < 0.01). Conclusion: Acute poisoning primarily affects the young and economically productive population. In the south Indian population, pesticides are still the major contributor though corrosives are a major contributor among children. Mortality is still significant, and GCS status admission is the only predictor of mortality. How to cite this article: Krishnasamy N, Narmadhalakshmi R, Parameshwari P, Jayalakshmi R, Lokesh R, Jayanthi R, et al. Determinants of Poison-related Mortality in Tertiary Care Hospital, South India. Indian J Crit Care Med 2024;28(4):329-335.

8.
World J Microbiol Biotechnol ; 40(6): 165, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38630187

ABSTRACT

Bacterial reduction of hexavalent chromium (VI) to chromium (III) is a sustainable bioremediation approach. However, the Cr(VI) containing wastewaters are often characterized with complex conditions such as high salt, alkaline pH and heavy metals which severely impact the growth and Cr(VI) reduction potential of microorganisms. This study investigated Cr(VI) reduction under complex haloalkaline conditions by an Alteromonas sp. ORB2 isolated from aerobic granular sludge cultivated from the seawater-microbiome. Optimum growth of Alteromonas sp. ORB2 was observed under haloalkaline conditions at 3.5-9.5% NaCl and pH 7-11. The bacterial growth in normal culture conditions (3.5% NaCl; pH 7.6) was not inhibited by 100 mg/l Cr(VI)/ As(V)/ Pb(II), 50 mg/l Cu(II) or 5 mg/l Cd(II). Near complete reduction of 100 mg/l Cr(VI) was achieved within 24 h at 3.5-7.5% NaCl and pH 8-11. Cr(VI) reduction by Alteromonas sp. ORB2 was not inhibited by 100 mg/L As(V), 100 mg/L Pb(II), 50 mg/L Cu(II) or 5 mg/L Cd(II). The bacterial cells grew in the medium with 100 mg/l Cr(VI) contained lower esterase activity and higher reactive oxygen species levels indicating toxicity and oxidative stress. In-spite of toxicity, the cells grew and reduced 100 mg/l Cr(VI) completely within 24 h. Cr(VI) removal from the medium was driven by bacterial reduction to Cr(III) which remained in the complex medium. Cr(VI) reduction was strongly linked to aerobic growth of Alteromonas sp. The Cr(VI) reductase activity of cytosolic protein fraction was pronounced by supplementing with NADPH in vitro assays. This study demonstrated a growth-dependent aerobic Cr(VI) reduction by Alteromonas sp. ORB2 under complex haloalkaline conditions akin to wastewaters.


Subject(s)
Alteromonas , Chromium , Metals, Heavy , Sodium Chloride/pharmacology , Cadmium , Lead/toxicity , Wastewater , Metals, Heavy/toxicity
9.
BMC Pregnancy Childbirth ; 24(1): 188, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38459455

ABSTRACT

BACKGROUND: India accounts for the largest number of global neonatal deaths with around 20 per 1000 live births. To improve the utilization of government services for institutional deliveries, Augmented Arogya Laxmi Scheme (ALS) was launched in Telangana state of southern India. This study assessed the effectiveness of the Janani Suraksha Yojana (JSY), which combines cash assistance with delivery and post-delivery care, in comparison to ALS in improving the outcomes related to antenatal, natal, and postnatal care in urban settlements of Hyderabad, Telangana, southern India. METHODS: This was a two-year cross-sectional study conducted in 14 urban settlements of Hyderabad city from September 2017- August 2019. All mothers delivered during the 18 months preceding the survey were enrolled after a written informed consent. Field investigators collected data on variables related to socio-demographic characteristics, awareness, and utilization of JSY and ALS programs. Variables related to antenatal history, antenatal care, complications during birth, delivery outcomes, newborn care, and postnatal care till 28 days were assessed. We used multivariable logistic regression model to examine the association between the different maternal, child, and socio-demographic characteristics of the two study groups. RESULTS: A total of 926 mothers were beneficiaries of Janani Suraksha Yojana (JSY) program while 933 mothers were beneficiaries of augmented Arogya Laxmi Scheme (ALS). Mothers in ALS group (AOR 1.71; 95% CI 1.21-2.43) were at increased odds of having more than eight antenatal care (ANC) visits compared to the mothers availing JSY. Mothers in ALS group were at decreased odds of having complications like severe pain in the abdomen (AOR 0.43; 95% CI 0.22-0.86), swelling of legs or feet (AOR 0.59; 95% CI 0.44-0.80) compared to mothers in JSY group. Children of mothers in the ALS group had increased odds of receiving breastfeeding within 30 minutes of birth (AOR 1.46; 95% CI 1.13-1.88) compared to children of mothers in JSY group. CONCLUSIONS: The newly launched augmented ALS led to the increased utilization of the government health facilities and improved the maternal and child health outcomes.


Subject(s)
Maternal Health Services , Infant, Newborn , Child , Pregnancy , Female , Humans , Cross-Sectional Studies , Prenatal Care , India/epidemiology , Outcome Assessment, Health Care , Delivery, Obstetric
10.
RSC Med Chem ; 15(3): 1022-1037, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38516592

ABSTRACT

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.

11.
J Trace Elem Med Biol ; 84: 127425, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38484635

ABSTRACT

BACKGROUND AND AIM: Diabetic kidney disease (DKD) is the primary cause of chronic kidney disease (CKD) worldwide. Altered mineral levels leading to adverse outcomes are widely reported in diabetes but limited in DKD, in the Indian scenario, hence this study was taken up to address this issue. METHODS: A hospital-based case-control study was taken up with 54 healthy controls (C) and 140 subjects with type 2 diabetes wherein 74 subjects with diabetes and CKD formed the DKD group, and 66 subjects with diabetes but no CKD formed the diabetic no-chronic kidney disease (DNCKD) group. High-resolution inductively coupled plasma mass spectrometry was used to evaluate the blood levels of minerals (calcium (Ca), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), and selenium (Se)), and a raw food-based food frequency questionnaire for dietary intakes. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (mL/min/1.73 m2) and albuminuria. Spearman's rank correlation was used to evaluate the relationship between the categorical variables. RESULTS: The median values of plasma Ca in the DKD group were significantly lower compared with the DNCKD and C groups (10.5 mg/dL vs. 11.0 mg/dL and 11.7 mg/dL, p<0.001). Furthermore, plasma Ca levels lowered with declining kidney function, as evidenced by the eGFR and albuminuria segregation. Dietary intake of minerals did not correlate with the corresponding plasma levels. However, in the DKD group, eGFR correlated positively with the plasma levels of Ca (r= 0.422, p=0.001), Cr (r= 0.351, p=0.008), Mn (r= 0.338, p=0.011), Fe (r= 0.403, p=0.002), Cu (r= 0.274, p=0.041) and negatively with Se (r= -0.486, p<0.001). CONCLUSION: Plasma Ca levels are lower in the DKD group with a strong positive association with eGFR, indicating its role in predicting the onset and progression of kidney function decline.


Subject(s)
Diabetes Mellitus, Type 2 , Minerals , Renal Insufficiency, Chronic , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Case-Control Studies , Male , Female , Renal Insufficiency, Chronic/blood , Middle Aged , Minerals/blood , Chromium/blood , Selenium/blood , Aged , Calcium/blood , Glomerular Filtration Rate
12.
Int J Obes (Lond) ; 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38504059

ABSTRACT

BACKGROUND: The prevalence of obesity is increasing worldwide at an alarming rate. In addition to the increased incidence of cardiovascular and metabolic diseases, obesity is the most potent risk factor for developing chronic kidney disease (CKD). Although systemic events such as hemodynamic factors, metabolic effects, and lipotoxicity were implicated in the pathophysiology of obesity-related glomerulopathy (ORG) and kidney dysfunction, the precise mechanisms underlying the association between obesity and CKD remain unexplored. METHODS: In this study, we employed spontaneous WNIN/Ob rats to investigate the molecular events that promote ORG. Further, we fed a high-fat diet to mice and analyzed the incidence of ORG. Kidney functional parameters, micro-anatomical manifestations, and podocyte morphology were investigated in both experimental animal models. Gene expression analysis in the rodents was compared with human subjects by data mining using Nephroseq and Kidney Precision Medicine Project database. RESULTS: WNIN/Ob rats were presented with proteinuria and several glomerular deformities, such as adaptive glomerulosclerosis, decreased expression of podocyte-specific markers, and effacement of podocyte foot process. Similarly, high-fat-fed mice also showed glomerular injury and proteinuria. Both experimental animal models showed increased expression of podocyte-specific transcription factor WT1. The altered expression of putative targets of WT1 such as E-cadherin, podocin (reduced), and α-SMA (increased) suggests elevated expression of WT1 in podocytes elicits mesenchymal phenotype. Curated data from CKD patients revealed increased expression of WT1 in the podocytes and its precursors, parietal epithelial cells. CONCLUSION: WT1 is crucial during nephron development and has minimal expression in adult podocytes. Our study discovered elevated expression of WT1 in podocytes in obesity settings. Our analysis suggests a novel function for WT1 in the pathogenesis of ORG; however, the precise mechanism of WT1 induction and its involvement in podocyte pathobiology needs further investigation.

13.
Graefes Arch Clin Exp Ophthalmol ; 262(7): 2247-2267, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38400856

ABSTRACT

BACKGROUND: Diabetic retinopathy (DR) is a serious eye complication that results in permanent vision damage. As the number of patients suffering from DR increases, so does the delay in treatment for DR diagnosis. To bridge this gap, an efficient DR screening system that assists clinicians is required. Although many artificial intelligence (AI) screening systems have been deployed in recent years, accuracy remains a metric that can be improved. METHODS: An enumerative pre-processing approach is implemented in the deep learning model to attain better accuracies for DR severity grading. The proposed approach is compared with various pre-trained models, and the necessary performance metrics were tabulated. This paper also presents the comparative analysis of various optimization algorithms that are utilized in the deep network model, and the results were outlined. RESULTS: The experimental results are carried out on the MESSIDOR dataset to assess the performance. The experimental results show that an enumerative pipeline combination K1-K2-K3-DFNN-LOA shows better results when compared with other combinations. When compared with various optimization algorithms and pre-trained models, the proposed model has better performance with maximum accuracy, precision, recall, F1 score, and macro-averaged metric of 97.60%, 94.60%, 98.40%, 94.60%, and 0.97, respectively. CONCLUSION: This study focussed on developing and implementing a DR screening system on color fundus photographs. This artificial intelligence-based system offers the possibility to enhance the efficacy and approachability of DR diagnosis.


Subject(s)
Algorithms , Diabetic Retinopathy , Severity of Illness Index , Humans , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/classification , Deep Learning , Artificial Intelligence , Retina/pathology , Retina/diagnostic imaging , Reproducibility of Results , Male
14.
PLoS Pathog ; 20(2): e1012045, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38416790

ABSTRACT

Protein ubiquitination is essential for cellular homeostasis and regulation of several processes, including cell division and genome integrity. Ubiquitin E3 ligases determine substrate specificity for ubiquitination, and Cullin-RING E3 ubiquitin ligases (CRLs) make the largest group among the ubiquitin E3 ligases. Although conserved and most studied in model eukaryotes, CRLs remain underappreciated in Plasmodium and related parasites. To investigate the CRLs of human malaria parasite Plasmodium falciparum, we generated parasites expressing tagged P. falciparum cullin-1 (PfCullin-1), cullin-2 (PfCullin-2), Rbx1 (PfRbx1) and Skp1 (PfSkp1). PfCullin-1 and PfCullin-2 were predominantly expressed in erythrocytic trophozoite and schizont stages, with nucleocytoplasmic localization and chromatin association, suggesting their roles in different cellular compartments and DNA-associated processes. Immunoprecipitation, in vitro protein-protein interaction, and ubiquitination assay confirmed the presence of a functional Skp1-Cullin-1-Fbox (PfSCF) complex, comprising of PfCullin-1, PfRbx1, PfSkp1, PfFBXO1, and calcyclin binding protein. Immunoprecipitation, sequence analysis, and ubiquitination assay indicated that PfCullin-2 forms a functional human CRL4-like complex (PfCRL4), consisting of PfRbx1, cleavage and polyadenylation specificity factor subunit_A and WD40 repeat proteins. PfCullin-2 knock-down at the protein level, which would hinder PfCRL4 assembly, significantly decreased asexual and sexual erythrocytic stage development. The protein levels of several pathways, including protein translation and folding, lipid biosynthesis and transport, DNA replication, and protein degradation were significantly altered upon PfCullin-2 depletion, which likely reflects association of PfCRL4 with multiple pathways. PfCullin-2-depleted schizonts had poorly delimited merozoites and internal membraned structures, suggesting a role of PfCRL4 in maintaining membrane integrity. PfCullin-2-depleted parasites had a significantly lower number of nuclei/parasite than the normal parasites, indicating a crucial role of PfCRL4 in cell division. We demonstrate the presence of functional CRLs in P. falciparum, with crucial roles for PfCRL4 in cell division and maintaining membrane integrity.


Subject(s)
Plasmodium falciparum , Ubiquitin-Protein Ligases , Humans , Cell Division , Cullin Proteins/metabolism , Plasmodium falciparum/genetics , Plasmodium falciparum/metabolism , Ubiquitin/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitination
15.
Heliyon ; 10(3): e25064, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38352738

ABSTRACT

Breast cancer remains a significant global health concern, necessitating the development of novel therapeutic approaches. In this study, we investigate the role of Eu3+ doped hydroxyapatite nanocomposites (Han: Eu3+) in the treatment of MCF7 and 4T1 breast cancer cell lines. Furthermore, we explored the structural and luminescent properties of these nanocomposites. Han: Eu3+ were synthesized using a modified co-precipitation method, and their morphology and crystal structure were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD) in which the average crystalline size of Han: Eu3+ was found to be 25 nm, rendering them suitable for cellular uptake and targeted therapy. To gain insights into the luminescent properties of Han: Eu3+, their excitation and emission spectra were recorded using photoluminescence spectrometer. The characteristic red emission of Eu3+ ions was observed upon excitation, validating the successful doping of Eu3+ into the Han lattice, which was confirmed by the CIE chromaticity coordinate study. These luminescent properties of Han: Eu3+ hold promise for potential applications in bioimaging. To evaluate the efficacy of Han: Eu3+ in breast cancer treatment, MCF7 and 4T1 cell lines were exposed to varying concentrations of the nanocomposites. Cell viability assays revealed a concentration-dependent reduction in cell viability, indicating the potential anticancer activity of Han: Eu3+. The findings of this study contribute to the expanding field of nanomedicine, bringing targeted breast cancer treatments and us closer to more effective.

16.
J Colloid Interface Sci ; 659: 718-727, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38211489

ABSTRACT

Herein, we present a novel microwave-assisted method for the synthesis of palladium nanoparticles (PdNPs) supported by Limonia acidissima Groff tree extract gum. The synthesized PdNPs were characterized using various analytical techniques, including FTIR, SEM, TEM, UV-visible, and powder XRD analyses. TEM and XRD analysis confirmed that the synthesized LAG-PdNPs are highly crystalline nature spherical shapes with an average size diameter of 7-9 nm. We employed these gum-capped PdNPs to investigate their peroxidase-like activity for colorimetric detection of hydrogen peroxide (H2O2) and glucose. The oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2, catalyzed by PdNPs, produces oxidation products quantified at 652 nm using spectrophotometry. The catalytic activity of PdNPs was optimized with respect to temperature and pH. The developed method exhibited a linear range of detection from 1 to 50 µm, with detection limits of 0.35 µm for H2O2 and 0.60 µm for glucose.


Subject(s)
Colorimetry , Metal Nanoparticles , Metal Nanoparticles/chemistry , Palladium/chemistry , Hydrogen Peroxide/analysis , Microwaves , Glucose/analysis
17.
Org Lett ; 26(2): 473-476, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38193732

ABSTRACT

Nitrosyl triflate is an excellent donor of NO+ to C═C and very unreactive benzenoids, in contrast to the much less reactive nitrosyl mesylate. However, both of these reagents are strongly activated by the bis-coordinating Lewis acids TiCl4 and SnCl4 and become super reactive NO+ donors. Strong catalysis and activation are even observed with the inherently less electrophilic nitrosyl trifluoroacetate. Monocoordinating strong Lewis acids, e.g., MeAlCl2, are relatively ineffective.

18.
Chem Biol Interact ; 390: 110889, 2024 Feb 25.
Article in English | MEDLINE | ID: mdl-38272248

ABSTRACT

The current study was designed to test a functional food (FF) mixture containing aldose reductase inhibitors and antiglycation bioactive compounds for suppressing the onset and progression of cataracts in a diabetic rat model. Two-month-old Sprague Dawley rats were grouped as control (C), diabetes untreated (D), and diabetic rats treated with FF at two doses (FF1 = 1.35 g and FF2 = 6.25 g/100g of diet). Diabetes was induced by a single injection of streptozotocin. The FF is a mixture of amla, turmeric, black pepper, cinnamon, ginger, and fenugreek added to the rodent diet. The status of cataracts was monitored weekly by a slit lamp examination for 20 weeks, after which animals were sacrificed to collect eye lenses. Feeding FF1 and FF2 to diabetic rats yielded a significant anti-hyperglycaemic effect and marginally prevented body weight loss. FF delayed cataract progression, and FF2 showed better efficacy than FF1. FF prevented the loss of lens crystallins and their insolubilization in diabetic rats. The antioxidant potential of FF was evident with the lowered protein carbonyls, lipid peroxidation, and prevention of altered antioxidant enzyme activities induced by diabetes. These studies demonstrate the efficacy of plant-derived dietary supplements against the onset and progression of cataracts in a well-established rat model of diabetic eye disease.


Subject(s)
Cataract , Diabetes Mellitus, Experimental , Lens, Crystalline , Rats , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Rodentia/metabolism , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Rats, Sprague-Dawley , Functional Food , Cataract/drug therapy , Cataract/prevention & control , Aldehyde Reductase/metabolism
19.
Int J Biol Macromol ; 259(Pt 1): 129105, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38176508

ABSTRACT

Microbial exopolysaccharides (EPS) are high molecular weight polymeric substances with great diversity and variety of applications in the food and pharma industry. In this study, we report the extraction of an EPS from Enterococcus hirae OL616073 strain originally isolated from Indian fermented food and its purification by ion exchange and size exclusion chromatography for physical-functional analyses. The EPS showed two prominent fractions (EPS F1 and EPS F2) with molecular mass 7.7 × 104 and 6.5 × 104 Da respectively by gel permeation chromatography. These fractions were further characterized by FTIR, HPTLC, GC-MS, and NMR as a homopolysaccharide of glucose linked with α-(1 â†’ 6) and α-(1 â†’ 3) glycosidic linkages. The porous, spongy, granular morphology of EPS was observed under scanning electron microscopy. EPS has revealed strong physico-functional properties like water solubility index (76.75 %), water contact angle (65.74°), water activity (0.35), hygroscopicity (3.05 %), water holding capacity (296.19 %), oil holding capacity (379.91 %), foaming capacity (19.58 %), and emulsifying activity (EA1-72.22 %). Rheological analysis showed that aqueous solution of EPS exhibited a non-Newtonian fluid behavior and shear-thinning characteristics. Overall, EPS exhibits techno functional properties with potential applications as a functional biopolymer in food and pharma industry.


Subject(s)
Enterococcus hirae , Glucans , Glucans/chemistry , Solubility , Molecular Weight , Water/chemistry , Polysaccharides, Bacterial/chemistry
20.
Chem Biol Interact ; 387: 110823, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38049026

ABSTRACT

Chronic hyperglycemia-induced neuropathological changes include neuronal apoptosis, astrogliosis, decrease in neurotrophic support, impaired synaptic plasticity, and impaired protein quality control (PQC) system. Vitamin B12 is indispensable for neuronal development and brain function. Several studies reported the neuroprotective effect of B12 supplementation in diabetic patients. However, the underlying molecular basis for the neuroprotective effect of B12 supplementation in diabetes needs to be thoroughly investigated. Two-month-old Sprague-Dawley rats were randomly assigned into three groups: Control (CN), diabetes (D; induced with streptozotocin; STZ), and diabetic rats supplemented with vitamin B12 (DBS; vitamin B12; 50 µg/kg) for four months. At the end of 4 months of experimentation, the brain was dissected to collect the cerebral cortex (CC). The morphology of CC was investigated with H&E and Nissl body staining. Neuronal apoptosis was determined with TUNEL assay. The components of neurotrophic support, astrogliosis, synaptic plasticity, and PQC processes were investigated by immunoblotting and immunostaining methods. H& E, Nissl body, and TUNEL staining revealed that diabetes-induced neuronal apoptosis and degeneration. However, B12 supplementation ameliorated the diabetes-induced neuronal apoptosis. Further, B12 supplementation restored the markers of neurotrophic support (BDNF, NGF, and GDNF), and synaptic plasticity (SYP, and PSD-95) in diabetic rats. Interestingly, B12 supplementation also attenuated astrogliosis, ER stress, and ameliorated autophagy-related proteins in diabetic rats. Overall, these findings suggest that B12 acts as a neuroprotective agent by inhibiting the neuropathological changes in STZ-induced type 1 diabetes. Thus, B12 supplementation could produce beneficial outcomes including neuroprotective effects in diabetic patients.


Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1 , Neuroprotective Agents , Rats , Humans , Animals , Infant , Vitamin B 12/pharmacology , Vitamin B 12/therapeutic use , Rats, Sprague-Dawley , Streptozocin/pharmacology , Diabetes Mellitus, Experimental/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Diabetes Mellitus, Type 1/chemically induced , Diabetes Mellitus, Type 1/drug therapy , Gliosis , Apoptosis
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