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1.
Brief Funct Genomics ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832682

ABSTRACT

Sesame (Sesamum indicum L.) is a globally cultivated oilseed crop renowned for its historical significance and widespread growth in tropical and subtropical regions. With notable nutritional and medicinal attributes, sesame has shown promising effects in combating malnutrition cancer, diabetes, and other diseases like cardiovascular problems. However, sesame production faces significant challenges from environmental threats such as charcoal rot, drought, salinity, and waterlogging stress, resulting in economic losses for farmers. The scarcity of information on stress-resistance genes and pathways exacerbates these challenges. Despite its immense importance, there is currently no platform available to provide comprehensive information on sesame, which significantly hinders the mining of various stress-associated genes and the molecular breeding of sesame. To address this gap, here a free, web-accessible, and user-friendly genomic web resource (SesameGWR, http://backlin.cabgrid.res.in/sesameGWR/) has been developed This platform provides key insights into differentially expressed genes, transcription factors, miRNAs, and molecular markers like simple sequence repeats, single nucleotide polymorphisms, and insertions and deletions associated with both biotic and abiotic stresses.. The functional genomics information and annotations embedded in this web resource were predicted through RNA-seq data analysis. Considering the impact of climate change and the nutritional and medicinal importance of sesame, this study is of utmost importance in understanding stress responses. SesameGWR will serve as a valuable tool for developing climate-resilient sesame varieties, thereby enhancing the productivity of this ancient oilseed crop.

2.
J Neurol ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730096

ABSTRACT

ELEVATE (Study 410; NCT03288129) is the first prospective, multicenter, open-label, Phase IV study of perampanel as monotherapy or first adjunctive therapy in patients aged ≥ 4 years with focal-onset seizures or generalized tonic-clonic seizures in the United States. The study included Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4 weeks) Periods. During Titration, perampanel was initiated at 2 mg/day and up-titrated to 4 mg/day at Week 3. Depending on response and tolerability, optional up-titrations to a maximum of 12 mg/day occurred. The primary endpoint was retention rate; additional endpoints included seizure-freedom rate, 50% responder rate, and incidence of treatment-emergent adverse events (TEAEs). At baseline, 10 (18.5%) patients were assigned to the monotherapy group and 44 (81.5%) patients to the first adjunctive therapy group. However, due to the addition of an anti-seizure medication along with perampanel on the first day of treatment, one patient was excluded from the monotherapy subgroup analyses. The mean perampanel exposure duration was 39.8 weeks and 32 (59.3%) patients completed the study. Retention rate at 12 months (or study completion) was 63.0% (monotherapy, 77.8%; first adjunctive therapy, 59.1%). Seizure-freedom rate during the Maintenance Period was 32.7% (monotherapy, 44.4%; first adjunctive therapy, 29.5%) and the 50% responder rate was 78.7% (monotherapy, 85.7%; first adjunctive therapy, 76.9%). TEAEs and serious TEAEs were reported by 88.9% (n = 48/54) and 7.4% (n = 4/54) of patients, respectively. Overall, the efficacy and safety of perampanel as monotherapy or first adjunctive therapy support the use of perampanel as early-line treatment for epilepsy.

3.
Curr Drug Targets ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38726782

ABSTRACT

The emergence of new variants of the SARS-CoV-2 virus during the COVID-19 pandemic has prompted significant developments in the understanding, monitoring, and response to these strains. This comprehensive review focuses on two prominent variants of interest (VoI), XBB. 1.5 (Kraken) and XBB.1.16 ("Arcturus"), along with seven variants under observation (VuM), including EG.5. The World Health Organization (WHO) identified these variants in July 2023, highlighting EG.5's noteworthy rise in prevalence. EG.5, also known as "Eris," has exhibited an increased effective reproductive rate, prompting concerns about its contagiousness and immune evasion capabilities. With an altered spike protein in the Receptor-Binding Domain (RBD), EG.5 shares similarities with XBB.1.5 but surpasses it in prevalence, constituting 20% of COVID-19 cases in the United States by late August. EG.5's subvariant, EG.5.1, poses challenges with mutations like Q52H and F456L, contributing to its ability to bypass neutralizing antibodies. The global distribution of SARS-CoV-2 variants presents a dynamic landscape, with XBB.1.16 and other strains gaining prominence. The advent of the BA.2.86 variant further complicates the scenario, with its notable spread in regions lacking robust viral surveillance. A thorough analysis of mutations reveals the evolving nature of the Omicron variant, with distinct amino acid changes characterizing XBB.1.5, XBB.1.16, and EG.5. The WHO designates EG.5 as a "variant of interest" due to its increased contagiousness and potential immune evasion, emphasizing the need for vigilant monitoring. The risk assessment of EG.5 underscores its rapid development and growing prevalence globally. While booster vaccines targeting XBB.1.5 are in development, antiviral medications like nirmatrelvir/ritonavir (Paxlovid) continue to exhibit efficacy. In the context of the evolving variants, the FDA has granted emergency use authorization for updated COVID-19 vaccines targeting circulating strains, reflecting the adaptability of vaccination strategies to address emerging challenges. This comprehensive overview provides a nuanced understanding of the diverse Omicron subvariants, their global impact, and the ongoing efforts to combat their spread through vaccination and therapeutic interventions.

4.
Chem Biol Drug Des ; 103(5): e14531, 2024 May.
Article in English | MEDLINE | ID: mdl-38726798

ABSTRACT

Inhibition of prolylhydroxylase-2 (PHD-2) in both normoxic and hypoxic cells is a critical component of solid tumours. The present study aimed to identify small molecules with PHD-2 activation potential. Virtually screening 4342 chemical compounds for structural similarity to R59949 and docking with PHD-2. To find the best drug candidate, hits were assessed for drug likeliness, antihypoxic and antineoplastic potential. The selected drug candidate's PHD-2 activation, cytotoxic and apoptotic potentials were assessed using 2-oxoglutarate, MTT, AO/EtBr and JC-1 staining. The drug candidate was also tested for its in-vivo chemopreventive efficacy against DMBA-induced mammary gland cancer alone and in combination with Tirapazamine (TPZ). Virtual screening and 2-oxoglutarate assay showed BBAP-6 as lead compound. BBAP-6 exhibited cytotoxic and apoptotic activity against ER+ MCF-7. In carmine staining and histology, BBAP-6 alone or in combination with TPZ restored normal surface morphology of the mammary gland after DMBA produced malignant alterations. Immunoblotting revealed that BBAP-6 reduced NF-κB expression, activated PHD-2 and induced intrinsic apoptotic pathway. Serum metabolomics conducted with 1H NMR confirmed that BBAP-6 prevented HIF-1α and NF-κB-induced metabolic changes in DMBA mammary gland cancer model. In a nutshell, it can be concluded that BBAP-6 activates PHD-2 and exhibits anticancer potential.


Subject(s)
Apoptosis , Breast Neoplasms , Hypoxia-Inducible Factor-Proline Dioxygenases , Humans , Female , Animals , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/prevention & control , Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism , Hypoxia-Inducible Factor-Proline Dioxygenases/antagonists & inhibitors , Apoptosis/drug effects , Mice , Cell Hypoxia/drug effects , Molecular Docking Simulation , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , MCF-7 Cells , Cell Line, Tumor , NF-kappa B/metabolism , Tirapazamine/pharmacology , Tirapazamine/chemistry , Tirapazamine/metabolism
5.
Sci Rep ; 14(1): 10675, 2024 05 09.
Article in English | MEDLINE | ID: mdl-38724667

ABSTRACT

Trillium govanianum is traditionally used to treat innumerable alignments like sexual disorders, cancer, inflammation etc. Mainly rhizomes of T. govanianum have been explored for phytochemical profiling but comprehensive metabolomics of other parts has not been yet deeply investigated. Thus, current study was aimed for organs-specific (roots, rhizomes, rhizomatous buds, stems, leaves, and fruits) phytochemical profiling of T. govanianum via metabolomics approach. Targeted (steroidal saponins and free sugars) and non-targeted metabolomics were performed by UPLC-PDA/ELSD & UHPLC-Q-TOF-IMS. Among steroidal compounds, 20-hydroxyecdysone, pennogenin-3-O-ß-chacotrioside, dioscin were found predominantly in all samples while diosgenin was identified only in rhizomes. Further, four free sugars viz. 2-deoxyribose (116.24 ± 1.26 mg/g: leaves), fructose (454.76 ± 12.14 mg/g: rhizomes), glucose (243.21 ± 7.53 mg/g: fruits), and galactose (69.06 ± 2.14 mg/g: fruits) were found significant in respective parts of T. govanianum. Elemental analysis of targeted samples was determined by atomic absorption spectrophotometer. Heavy metals (Cd, Hg, Pd, As) were absent while micro- (Mn, Na, Zn, Cu) and macro- (Ca, Fe, Mg, K) elements were found in all samples. Furthermore, UHPLC-Q-TOF-IMS had identified 103 metabolites based on their mass fragmentation patterns and 839 were tentatively predicted using METLIN database. The multivariate statistical analysis showed organs specific clustering and variance of metabolites. Apart from this, extracts were evaluated for in vitro anticholinesterase activity, and found potentials inhibitors with IC50 values 2.02 ± 0.15 to 27.65 ± 0.89 mg/mL and 3.58 ± 0.12 to 16.81 ± 2.48 mg/mL of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme, respectively. Thus, comprehensive metabolomics and anti-cholinesterase activity of different parts of T. govanianum would lay the foundation for improving medicinal importance and health benefits of T. govanianum.


Subject(s)
Cholinesterase Inhibitors , Metabolomics , Trillium , Metabolomics/methods , Cholinesterase Inhibitors/pharmacology , Trillium/chemistry , Trillium/metabolism , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Leaves/chemistry , Plant Leaves/metabolism , Phytochemicals/pharmacology , Phytochemicals/chemistry , Phytochemicals/metabolism , Phytochemicals/analysis , Chromatography, High Pressure Liquid , Rhizome/chemistry , Plant Roots/chemistry , Plant Roots/metabolism
6.
Biotechnol Biofuels Bioprod ; 17(1): 72, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811976

ABSTRACT

Succinic acid (SA) is one of the top platform chemicals with huge applications in diverse sectors. The presence of two carboxylic acid groups on the terminal carbon atoms makes SA a highly functional molecule that can be derivatized into a wide range of products. The biological route for SA production is a cleaner, greener, and promising technological option with huge potential to sequester the potent greenhouse gas, carbon dioxide. The recycling of renewable carbon of biomass (an indirect form of CO2), along with fixing CO2 in the form of SA, offers a carbon-negative SA manufacturing route to reduce atmospheric CO2 load. These attractive attributes compel a paradigm shift from fossil-based to microbial SA manufacturing, as evidenced by several commercial-scale bio-SA production in the last decade. The current review article scrutinizes the existing knowledge and covers SA production by the most efficient SA producers, including several bacteria and yeast strains. The review starts with the biochemistry of the major pathways accumulating SA as an end product. It discusses the SA production from a variety of pure and crude renewable sources by native as well as engineered strains with details of pathway/metabolic, evolutionary, and process engineering approaches for enhancing TYP (titer, yield, and productivity) metrics. The review is then extended to recent progress on separation technologies to recover SA from fermentation broth. Thereafter, SA derivatization opportunities via chemo-catalysis are discussed for various high-value products, which are only a few steps away. The last two sections are devoted to the current scenario of industrial production of bio-SA and associated challenges, along with the author's perspective.

7.
Eur J Pharm Biopharm ; 199: 114311, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38710374

ABSTRACT

The field of machine learning (ML) is advancing to a larger extent and finding its applications across numerous fields. ML has the potential to optimize the development process of microneedle patch by predicting the drug release pattern prior to its fabrication and production. The early predictions could not only assist the in-vitro and in-vivo experimentation of drug release but also conserve materials, reduce cost, and save time. In this work, we have used a dataset gleaned from the literature to train and evaluate different ML models, such as stacking regressor, artificial neural network (ANN) model, and voting regressor model. In this study, models were developed to improve prediction accuracy of the in-vitro drug release amount from the hydrogel-type microneedle patch and the in-vitro drug permeation amount through the micropores created by solid microneedles on the skin. We compared the performance of these models using various metrics, including R-squared score (R2 score), root mean squared error (RMSE), and mean absolute error (MAE). Voting regressor model performed better with drug permeation percentage as an outcome feature having RMSE value of 3.24. In comparison, stacking regressor have a RMSE value of 16.54, and ANN model has shown a RMSE value of 14. The value of permeation amount calculated from the predicted percentage is found to be more accurate with RMSE of 654.94 than direct amount prediction, having a RMSE of 669.69. All our models have performed far better than the previously developed model before this research, which had a RMSE of 4447.23. We then optimized voting regressor model's hyperparameter and cross validated its performance. Furthermore, it was deployed in a webapp using Flask framework, showing a way to develop an application to allow other users to easily predict drug permeation amount from the microneedle patch at a particular time period. This project demonstrates the potential of ML to facilitate the development of microneedle patch and other drug delivery systems.


Subject(s)
Drug Delivery Systems , Machine Learning , Needles , Neural Networks, Computer , Permeability , Skin Absorption , Skin , Skin Absorption/physiology , Drug Delivery Systems/methods , Skin/metabolism , Administration, Cutaneous , Drug Liberation , Transdermal Patch , Animals , Microinjections/methods , Microinjections/instrumentation
8.
Arch Microbiol ; 206(6): 272, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38772980

ABSTRACT

Phage-encoded endolysins have emerged as a potential substitute to conventional antibiotics due to their exceptional benefits including host specificity, rapid host killing, least risk of resistance. In addition to their antibacterial potency and biofilm eradication properties, endolysins are reported to exhibit synergism with other antimicrobial agents. In this study, the synergistic potency of endolysins was dissected with antimicrobial peptides to enhance their therapeutic effectiveness. Recombinantly expressed and purified bacteriophage endolysin [T7 endolysin (T7L); and T4 endolysin (T4L)] proteins have been used to evaluate the broad-spectrum antibacterial efficacy using different bacterial strains. Antibacterial/biofilm eradication studies were performed in combination with different antimicrobial peptides (AMPs) such as colistin, nisin, and polymyxin B (PMB) to assess the endolysin's antimicrobial efficacy and their synergy with AMPs. In combination with T7L, polymyxin B and colistin effectively eradicated the biofilm of Pseudomonas aeruginosa and exhibited a synergistic effect. Further, a combination of T4L and nisin displayed a synergistic effect against Staphylococcus aureus biofilms. In summary, the obtained results endorse the theme of combinational therapy consisting of endolysins and AMPs as an effective remedy against the drug-resistant bacterial biofilms that are a serious concern in healthcare settings.


Subject(s)
Anti-Bacterial Agents , Antimicrobial Peptides , Biofilms , Drug Synergism , Endopeptidases , Microbial Sensitivity Tests , Pseudomonas aeruginosa , Staphylococcus aureus , Biofilms/drug effects , Endopeptidases/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Pseudomonas aeruginosa/drug effects , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry , Nisin/pharmacology , Nisin/chemistry , Polymyxin B/pharmacology , Bacteriophages , Colistin/pharmacology , Bacteriophage T4/drug effects , Bacteriophage T4/physiology , Bacteriophage T7/drug effects , Bacteriophage T7/genetics
9.
J Proteomics ; 302: 105200, 2024 May 19.
Article in English | MEDLINE | ID: mdl-38772440

ABSTRACT

BACKGROUND AND AIMS: Postmenopausal osteoporosis (PMO) and type 2 diabetes mellitus (T2DM) frequently coexist in postmenopausal women. The study aimed to explore metabolic variations linked to these circumstances and their simultaneous presence through proton nuclear magnetic resonance metabolomics (1H NMR). MATERIALS AND METHODS: Serum samples from 80 postmenopausal women, including 20 PMO individuals, 20 T2DM, 20 T2DM + PMO, and 20 healthy postmenopausal women, were analyzed using 1H NMR spectroscopy. RESULTS: Our study revealed significant metabolic profile differences among the four groups. Notably, the T2DM + PMO group showed elevated levels of alanine, pyruvate, glutamate, lactate, and aspartate, indicating their involvement in lipid metabolism, energy, and amino acids. Importantly, our multivariate statistical analysis identified a metabolite set that accurately distinguished the groups, suggesting its potential as an early diagnostic marker. CONCLUSION: The 1H NMR metabolomics approach uncovered metabolic biomarkers intricately linked to postmenopausal osteoporosis (PMO), type 2 diabetes mellitus (T2DM), and their concurrent presence. Among these biomarkers, alanine emerged as a pivotal player, showing its significant role in the metabolic landscape associated with PMO and T2DM. These findings shed light on the pathophysiological mechanisms underlying these conditions and underscore alanine's potential as a diagnostic biomarker.

10.
Pathol Res Pract ; 258: 155303, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38728793

ABSTRACT

Hepatocellular carcinoma (HCC) is among the primary reasons for fatalities caused by cancer globally, highlighting the need for comprehensive knowledge of its molecular aetiology to develop successful treatment approaches. The PI3K/Akt system is essential in the course of HCC, rendering it an intriguing candidate for treatment. Non-coding RNAs (ncRNAs), such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are important mediators of the PI3K/Akt network in HCC. The article delves into the complex regulatory functions of ncRNAs in influencing the PI3K/Akt system in HCC. The study explores how lncRNAs, miRNAs, and circRNAs impact the expression as well as the function of the PI3K/Akt network, either supporting or preventing HCC growth. Additionally, treatment strategies focusing on ncRNAs in HCC are examined, such as antisense oligonucleotide-based methods, RNA interference, and small molecule inhibitor technologies. Emphasizing the necessity of ensuring safety and effectiveness in clinical settings, limitations, and future approaches in using ncRNAs as therapies for HCC are underlined. The present study offers useful insights into the complex regulation system of ncRNAs and the PI3K/Akt cascade in HCC, suggesting possible opportunities for developing innovative treatment approaches to address this lethal tumor.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , RNA, Untranslated , Signal Transduction , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , Signal Transduction/genetics , RNA, Untranslated/genetics , Gene Expression Regulation, Neoplastic/genetics , RNA, Circular/genetics , RNA, Circular/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
11.
Comput Methods Programs Biomed ; 250: 108195, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38692251

ABSTRACT

BACKGROUND AND OBJECTIVE: Timely stroke treatment can limit brain damage and improve outcomes, which depends on early recognition of the symptoms. However, stroke cases are often missed by the first respondent paramedics. One of the earliest external symptoms of stroke is based on facial expressions. METHODS: We propose a computerized analysis of facial expressions using action units to distinguish between Post-Stroke and healthy people. Action units enable analysis of subtle and specific facial movements and are interpretable to the facial expressions. The RGB videos from the Toronto Neuroface Dataset, which were recorded during standard orofacial examinations of 14 people with post-stroke (PS) and 11 healthy controls (HC) were used in this study. Action units were computed using XGBoost which was trained using HC, and classified using regression analysis for each of the nine facial expressions. The analysis was performed without manual intervention. RESULTS: The results were evaluated using leave-one-our validation. The accuracy was 82% for Kiss and Spread, with the best sensitivity of 91% in the differentiation of PS and HC. The features corresponding to mouth muscles were most suitable. CONCLUSIONS: This pilot study has shown that our method can detect PS based on two simple facial expressions. However, this needs to be tested in real-world conditions, with people of different ethnicities and smartphone use. The method has the potential for a computerized assessment of the videos for use by the first respondents using a smartphone to perform screening tests, which can facilitate the timely start of the treatment.


Subject(s)
Facial Expression , Stroke , Humans , Pilot Projects , Female , Male , Middle Aged , Aged , Case-Control Studies , Video Recording
12.
Mol Pharm ; 21(6): 3061-3076, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38757678

ABSTRACT

Melanoma, characterized as the most aggressive and metastatic form of skin cancer, currently has limited treatment options, predominantly chemotherapy and radiation therapy. However, the drawbacks associated with parenterally administered chemotherapy underscore the urgent need for alternative compounds to combat melanoma effectively. Hesperidin (HES), a flavonoid present in various citrus fruits, exhibits promising anticancer activity. Nevertheless, the clinical utility of HES is hindered by challenges such as poor water solubility, a short half-life, and low oral bioavailability. In response to these limitations, we introduced a novel approach by formulating HES-loaded exosomes (Exo-HES). Isolation of exosomes was achieved through the ultracentrifugation method, and HES was efficiently loaded using the sonication method. The resulting formulations displayed a desirable particle size (∼106 nm) and exhibited a spherical morphology, as confirmed by scanning electron and atomic force microscopy. In vitro studies conducted on B16F10 cell lines demonstrated higher cytotoxicity of Exo-HES compared to free HES, supported by enhanced cellular uptake validated through coumarin-6-loaded exosomes. This superior cytotoxicity was further evidenced by DNA fragmentation, increased generation of free radicals (ROS), loss of mitochondrial membrane potential, and effective inhibition of colony formation. The antimetastatic properties of Exo-HES were confirmed through wound healing and transwell migration assays. Oral pharmacokinetics studies revealed a remarkable increase of approximately 2.5 times in oral bioavailability and half-life of HES when loaded into exosomes. Subsequent in vivo experiments utilizing a B16F10-induced melanoma model in Swiss mice established that Exo-HES exhibited superior anticancer activity compared to HES after oral administration. Importantly, no biochemical, hematological, or histological toxicities were observed in tumor-bearing mice treated with Exo-HES. These findings suggest that exosomes loaded with HES represent a promising nanocarrier strategy to enhance the therapeutic effectiveness of hesperidin in melanoma treatment.


Subject(s)
Exosomes , Hesperidin , Hesperidin/chemistry , Hesperidin/pharmacology , Hesperidin/administration & dosage , Hesperidin/pharmacokinetics , Animals , Mice , Cell Line, Tumor , Melanoma, Experimental/drug therapy , Melanoma, Experimental/pathology , Melanoma/drug therapy , Melanoma/pathology , Humans , Membrane Potential, Mitochondrial/drug effects , Male , Mice, Inbred C57BL , Drug Delivery Systems/methods
13.
Cureus ; 16(4): e58168, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38741883

ABSTRACT

Background This study aimed to observe the neurophysiological severity grading of carpel tunnel syndrome (CTS) using nerve conduction studies (NCSs) and the correlation between Tinel's and Phalen's signs. Methodology In this cross-sectional study, 240 patients of CTS were enrolled. NCSs were conducted in 480 hands. Various variables such as distal latency, amplitude, and nerve conduction velocity in both sensory and motor median nerves were recorded. The provocative tests capable of reproducing patients' symptoms such as Phalen's test and Tinel's test were performed on all 480 hands studied. Results Neurophysiological variables were affected in 449 out of 480 hands. Tinel's sign was observed in 59% of cases (265 hands) while Phalen's sign was positive in 37.2% (167 hands) of cases. Severity grading of CTS based on neurophysiological variables resulted in Grade I (mild) in 202 hands, Grade II (mild to moderate) in 56 hands, Grade III (moderate) in 39 hands, and Grade IV (severe) in 152 hands. Provocative tests (Tinel's and Phalen's) used for the diagnosis of CTS were positive in 68 hands (36.66%) and 26 hands (12.8%), respectively, in mild Grade I. However, as the CTS severity grade increased, the provocative test success rate also increased simultaneously. In severe Grade IV CTS, Tinel's and Phalen's tests were positive in 134 (88.1%) hands and 94 (61.8%) hands, respectively. Conclusions This study underscores the unreliability of Tinel's and Phalen's signs as screening methods for CTS severity. With moderate sensitivity and specificity, NCSs are deemed essential for confirming CTS diagnosis and assessing severity, especially in mild cases that might be mistakenly perceived as normal hands by consultants.

14.
Soft Matter ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38738579

ABSTRACT

The goal of this review is to present enzymosomes as an innovative means for site-specific drug delivery. Enzymosomes make use of an enzyme's special characteristics, such as its capacity to accelerate the reaction rate and bind to a particular substrate at a regulated rate. Enzymosomes are created when an enzyme forms a covalent linkage with a liposome or lipid vesicle surface. To construct enzymosomes with specialized activities, enzymes are linked using acylation, direct conjugation, physical adsorption, and encapsulation techniques. By reducing the negative side effects of earlier treatment techniques and exhibiting efficient medication release, these cutting-edge drug delivery systems improve long-term sickness treatments. They could be a good substitute for antiplatelet medication, gout treatment, and other traditional medicines. Recently developed supramolecular vesicular delivery systems called enzymosomes have the potential to improve drug targeting, physicochemical characteristics, and ultimately bioavailability in the pharmaceutical industry. Enzymosomes have advantages over narrow-therapeutic index pharmaceuticals as focusing on their site of action enhances both their pharmacodynamic and pharmacokinetic profiles. Additionally, it reduces changes in normal enzymatic activity, which enhances the half-life of an enzyme and accomplishes enzyme activity on specific locations.

15.
Toxicol Res (Camb) ; 13(3): tfae074, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38765239

ABSTRACT

Aim: The study investigated Ethion-induced developmental toxicity in Wistar albino rats and the potential ameliorative effects of quercetin and nano-quercetin co-administration. Further, In-silico docking of Ethion and quercetin with MCL-1 was conducted. Methodology: Quercetin nanoparticles were synthesized by ionic-gelation method. The encapsulated quercetin nanoparticles were characterized for Zeta size, UV-Vis spectroscopy, encapsulation efficiency, and TEM studies. Male rats were administered Ethion (high/low dose), quercetin, and nano-quercetin alone or in combination for 60 days. Female rats were introduced for mating on the 61st day, and pregnant females were observed for 20 gestational days. On GD 20, rats were sacrificed and evaluated for body/organ weight, reproductive indices, fetal morphology, skeletal, and visceral deformities.In silico binding energies of ethion and quercetin with MCL-1 were determined. Results: Nanoparticle size was 363.2 ± 1.23 nm on day 0 and 385.63 ± 1.53 nm on day 60, with PDI of 0.247 and charge of 22.9 mV. Absorbance maxima were at 374 nm, with encapsulation efficacy of 85.16 ± 0.33%. EHD male crossed females showed decreased body/organ weights, reduced fertility, hematoma, cleft palate, tail curling, and absence of extremity. Nano-quercetin co-administration normalized parameters comparable to controls. Both Ethion and quercetin interacted with MCL-1, with quercetin exhibiting stronger binding energy. Conclusion: Nano-quercetin demonstrated stronger antioxidant properties than quercetin, counteracting ethion-induced maternal/fetal abnormalities.

16.
J Pharm Bioallied Sci ; 16(Suppl 1): S979-S982, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38595578

ABSTRACT

In this case report, a 27-year-old woman who had pre-eclampsia in the past and had a cesarean section as a result of the condition presents with an uncommon and difficult form of postpartum paraplegia. She experienced bilateral lower limb paralysis and urine incontinence soon after the surgery, which quickly led to unconsciousness and required mechanical ventilator support and intensive care treatment. Comprehensive diagnostic testing, which included magnetic resonance imaging scans of the brain and spinal cord, identified signs typical of "Posterior Reversible Encephalopathy Syndrome (PRES)" and spinal cord infarction affecting segments C3 to D2. "Antiphospholipid Antibody Syndrome (APLA)" was identified by laboratory testing, highlighting the significance of taking a thorough approach to comprehending this uncommon clinical condition. Treatment included anticoagulant therapy, high-dose steroid therapy, and antihypertensive drugs, emphasizing the crucial importance of inter-disciplinary care in handling such complex situations. Even if the patient's symptoms have partially improved, their condition is still being closely monitored in the intensive care unit. In the context of postpartum neurological problems and the complex interplay between pre-eclampsia, spinal cord infarction, and related clinical symptoms, this case emphasizes the need for increased awareness and prompt management.

17.
Indian J Community Med ; 49(2): 342-348, 2024.
Article in English | MEDLINE | ID: mdl-38665468

ABSTRACT

Background: Ayushman Bharat-Pradhan Mantri Jan Aarogya Yojna (AB-PMJAY) as a financial risk protection scheme intends to reduce catastrophic health expenditure (CHE), especially among poor. The current study was carried out to assess the utility of AB-PMJAY in terms of reduction in CHE from before and after admission in a tertiary hospital in the northern state of India. Methodology: It was a hospital-based cross-sectional study carried out from August 2020 to October 2021 at a public tertiary hospital of Himachal Pradesh, India. Data were collected from surgery- and medicine-allied (SA and MA) specialties. Along with socio-demographic details, information for total monthly family expenditure (TMFE), out-of-pocket expenditure (OOPE), and indirect illness-related expenditure (IIE) was recorded before and after hospital admission. CHE was considered as more than 10.0% OOPE of THFE and more than 40.0% of capacity to pay (CTP). Results: A total of 336 participants with a mean age of 46 years were recruited (MA: 54.6%). The majority (~93.0%) of participants had illness of fewer than 6 months. The mean TMFE was observed to be INR 4213.1 (standard deviation: 2483.7) and found to be similar across specialties. The OOPE share of TMFE declined from 76.1% (before admission) to 30.0% (after admission). Before admission, CHE was found among 65.5% (10.0% of THFE) and 54.2% (40.0% of CTP) participants. It reduced to about 29.0% (based on both THE and CTP) after admission to hospital. Conclusion: AB-PMJAY scheme found to be useful in reducing CHE in a tertiary hospital.

18.
iScience ; 27(4): 109523, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38577103

ABSTRACT

Fabrication of stimuli-responsive superstructure capable of delivering chemotherapeutics directly to the cancer cell by sparing healthy cells is crucial. Herein, we developed redox-responsive hollow spherical assemblies through self-assembly of disulfide-linked cysteine-diphenylalanine (SN). These fluorescent hollow spheres display intrinsic green fluorescence, are proteolytically stable and biocompatible, and allow for real-time monitoring of their intracellular entry. The disulfide bond facilitates selective degradation in the presence of high glutathione (GSH) concentrations, prevalent in cancer cells. We achieved efficient encapsulation (68.72%) of the anticancer drug doxorubicin (Dox) and demonstrated GSH-dependent, redox-responsive drug release within cancerous cells. SN-Dox exhibited a 20-fold lower effective concentration (2.5 µM) for compromising breast cancer cell viability compared to non-malignant cells (50 µM). The ability of SN-Dox to initiate DNA damage signaling and trigger apoptosis was comparable to that of the unencapsulated drug. Our findings highlight the potential of SN for creating site-specific drug delivery vehicles for sustained therapeutic release.

19.
J Coll Physicians Surg Pak ; 34(4): 484-488, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38576295

ABSTRACT

OBJECTIVE: To analyse quantitatively the adequacy of demographics of clinical information and highlight specific areas of neglect, by assessing the adequacy of filling out histopathology request forms. STUDY DESIGN: Clinical Audit. Place and Duration of the Study: Department of Pathology, Dow University of Health Sciences (DUHS), Karachi, Pakistan, from January to September 2021. METHODOLOGY: A retrospective audit was carried out on the request forms of surgically resected tumours and biopsies. The recorded details of the patients' demographics and biopsy, clinical history and examination, and intraoperative findings were analysed. RESULTS: Out of 175 forms, patients' names were written in 174 (99.4%) while medical record numbers were written in 113 (64.6%). The doctors' names were given in 172 (98.3%) forms and phone numbers in 34 (19.4%). A clinical diagnosis was provided in 164 (93.7%) forms, while 152 (86.9%) forms correctly entered the biopsy site. Sixty-seven (38.3%) forms included the correct nature of the biopsy. Relevant operative details were provided in half of the forms. Symptoms and their duration were mentioned in 144 (82.3%) and 100 (57.1%), respectively. The form-filling rate was the same for both benign and malignant tumours. CONCLUSION: This study shows that in a significant proportion of cases, complete relevant information is not provided to the histopathologists on request forms for logistics. KEY WORDS: Histopathology, Request forms, Tumours, Audit.


Subject(s)
Neoplasms , Physicians , Humans , Pathologists , Retrospective Studies , Biopsy
20.
Indian J Pharmacol ; 56(2): 120-128, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38687316

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of topical nanoemulsion (NE)-loaded cream and gel formulations of Hippophae rhamnoides L. (sea buckthorn [SBT]) fruit oil for wound healing. MATERIALS AND METHODS: The NE-loaded cream and gel formulations of H. rhamnoides L. (SBT) fruit oil (IPHRFH) were prepared and evaluated for their wound-healing activity on female Sprague-Dawley (SD) rats. They were further divided into groups (seven) and the wound-healing activity was determined by measuring the area of the wound on the wounding day and on the 0th, 4th, 8th, and 10th days. The acute dermal toxicity of the formulations was assessed by observing the erythema, edema, and body weight (BW) of the rats. RESULTS: The topical NE cream and gel formulations of H. rhamnoides L. (SBT) fruit oil showed significant wound-healing activity in female SD rats. The cream formulation of IPHRFH showed 78.96%, the gel showed 72.59% wound contraction on the 8th day, whereas the positive control soframycin (1% w/w framycetin) had 62.29% wound contraction on the 8th day. The formulations also showed a good acute dermal toxicity profile with no changes significantly affecting BW and dermal alterations. CONCLUSIONS: The results of this study indicate that topical NE-loaded cream and gel formulation of H. rhamnoides L. (SBT) fruit oil are safe and effective for wound healing. The formulations showed no signs of acute dermal toxicity in female SD rats.


Subject(s)
Emulsions , Gels , Hippophae , Plant Oils , Rats, Sprague-Dawley , Wound Healing , Animals , Female , Hippophae/chemistry , Hippophae/toxicity , Wound Healing/drug effects , Rats , Plant Oils/toxicity , Plant Oils/administration & dosage , Fruit , Skin/drug effects , Administration, Cutaneous , Administration, Topical , Nanoparticles/toxicity
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