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1.
Gut Microbes ; 16(1): 2353394, 2024.
Article in English | MEDLINE | ID: mdl-38743047

ABSTRACT

Exposing C-section infants to the maternal vaginal microbiome, coined "vaginal seeding", partially restores microbial colonization. However, whether vaginal seeding decreases metabolic disease risk is unknown. Therefore, we assessed the effect of vaginal seeding of human infants on adiposity in a murine model. Germ-free mice were colonized with transitional stool from human infants who received vaginal seeding or control (placebo) seeding in a double-blind randomized trial. There was a reduction in intraabdominal adipose tissue (IAAT) volume in male mice that received stool from vaginally seeded infants compared to control infants. Higher levels of isoleucine and lower levels of nucleic acid metabolites were observed in controls and correlated with increased IAAT. This suggests that early changes in the gut microbiome and metabolome caused by vaginal seeding have a positive impact on metabolic health.


Subject(s)
Adiposity , Fecal Microbiota Transplantation , Feces , Gastrointestinal Microbiome , Vagina , Animals , Humans , Female , Mice , Male , Vagina/microbiology , Feces/microbiology , Feces/chemistry , Double-Blind Method , Intra-Abdominal Fat/metabolism , Infant , Infant, Newborn
2.
Nat Rev Nephrol ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719971

ABSTRACT

The ability to localize hundreds of macromolecules to discrete locations, structures and cell types in a tissue is a powerful approach to understand the cellular and spatial organization of an organ. Spatially resolved transcriptomic technologies enable mapping of transcripts at single-cell or near single-cell resolution in a multiplex manner. The rapid development of spatial transcriptomic technologies has accelerated the pace of discovery in several fields, including nephrology. Its application to preclinical models and human samples has provided spatial information about new cell types discovered by single-cell sequencing and new insights into the cell-cell interactions within neighbourhoods, and has improved our understanding of the changes that occur in response to injury. Integration of spatial transcriptomic technologies with other omics methods, such as proteomics and spatial epigenetics, will further facilitate the generation of comprehensive molecular atlases, and provide insights into the dynamic relationships of molecular components in homeostasis and disease. This Review provides an overview of current and emerging spatial transcriptomic methods, their applications and remaining challenges for the field.

3.
Mycoses ; 67(5): e13730, 2024 May.
Article in English | MEDLINE | ID: mdl-38712824

ABSTRACT

BACKGROUND: Due to a delay in diagnosis by conventional techniques and high mortality, the development of a standardised and rapid non-culture-based technique is an unmet need in pulmonary, gastrointestinal, and disseminated forms of mucormycosis. Though limited studies have been conducted for molecular diagnosis, there are no established serologic tests for this highly fatal infection. OBJECTIVE: To develop and evaluate an indirect in-house enzyme-linked immunosorbent assay (ELISA) utilising antigens of Rhizopus arrhizus for detecting anti-Rhizopus antibodies (IgG and IgM) in sera of patients with mucormycosis. METHODS: We extracted both secretory and mycelial Rhizopus antigens using standardised protocols. Bradford assay was used for protein quantification. We then standardised an indirect ELISA using R. arrhizus mycelial and secretory antigens (10.0 µg/mL in bicarbonate buffer pH 9.2) for detecting anti-Rhizopus IgG and IgM antibodies in patient sera. We included patients with mucormycosis, other fungal infections, and healthy controls. Antibody index value (E-value) was calculated for each patient sample. RESULTS: Asparagine broth culture filtrate utilising 85% ammonium sulphate salt fractionation and mycelial homogenate grown in yeast extract peptone dextrose (YPD) broth precipitated with trichloroacetic acid (TCA) yielded a large amount of good-quality protein for the assay. We included 55 patients with mucormycosis (rhino-orbito-cerebral mucormycosis [ROCM, n = 39], pulmonary [n = 15], gastrointestinal [n = 1]), 24 with other fungal infections (probable aspergillosis [n = 14], candidiasis [n = 10]), and healthy controls (n = 16). The sensitivity of the antibody test for diagnosing mucormycosis ranged from 83.6-92.7% for IgG and 72.7-87.3% for IgM, with a specificity of 91.7-92.5% for IgG and 80-82.5% for IgM. The sera from patients with other fungal infections and healthy individuals did not show significant cross-reactivity. CONCLUSION: The detection of anti-Rhizopus IgG antibody performed significantly better in comparison to IgM-based ELISA for diagnosing both ROCM (sensitivity of 84.6% vs. 69.2%) and pulmonary cases (86.6% vs. 80.0%). More extensive studies are required to confirm our findings.


Subject(s)
Antibodies, Fungal , Antigens, Fungal , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G , Immunoglobulin M , Mucormycosis , Rhizopus , Sensitivity and Specificity , Serologic Tests , Mucormycosis/diagnosis , Mucormycosis/microbiology , Mucormycosis/immunology , Humans , Rhizopus/immunology , Enzyme-Linked Immunosorbent Assay/methods , Antigens, Fungal/immunology , Antigens, Fungal/analysis , Serologic Tests/methods , Antibodies, Fungal/blood , Immunoglobulin M/blood , Immunoglobulin G/blood , Female , Male , Middle Aged
4.
J Assoc Physicians India ; 72(1): 63-73, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38736076

ABSTRACT

Heart failure (HF) is a global health concern that is prevalent in India as well. HF is reported at a younger age in Indian patients with comorbidity of type 2 diabetes (T2DM) in approximately 50% of patients. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), originally approved for T2DM, are new guideline-recommended and approved treatment strategies for HF. Extensive evidence highlights that SGLT2i exhibits profound cardiovascular (CV) benefits beyond glycemic control. SGLT2i, in conjunction with other guideline-directed medical therapies (GMDT), has additive effects in improving heart function and reducing adverse HF outcomes. The benefits of SGLT2i are across a spectrum of patients, with and without diabetes, suggesting their potential place in broader HF populations irrespective of ejection fraction (EF). This consensus builds on the updated evidence of the efficacy and safety of SGLT2i in HF and recommends its place in therapy with a focus on Indian patients with HF.


Subject(s)
Diabetes Mellitus, Type 2 , Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Heart Failure/drug therapy , India , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications
5.
Trauma Case Rep ; 51: 101014, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38623090

ABSTRACT

Child abuse is a matter of serious concern that can often result in devastating injuries. Incidence of spinal injuries from child abuse has been reported in <1-3 % of spinal injury cases. In the present study, a case of thoracolumbar translational injury (AO type C) is presented following an incidence of child abuse in a 2-year-old female. After successful management with operative fixation, the child showed a remarkable recovery in her neurological function with ambulatory power.

6.
Res Sq ; 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38562706

ABSTRACT

Tuberculosis (TB) remains a leading cause of death, but antibiotic treatments for tuberculous meningitis, the deadliest form of TB, are based on those developed for pulmonary TB and not optimized for brain penetration. Here, we performed first-in-human dynamic 18F-pretomanid positron emission tomography (PET) studies in eight human subjects for three-dimensional, multi-compartmental in situ visualization of antibiotic concentration-time exposures (area under the curve - AUC), demonstrating preferential brain (AUCtissue/plasma 2.25) versus lung (AUCtissue/plasma 0.97) tissue partitioning. Preferential, antibiotic-specific partitioning into brain or lung tissues of antibiotics active against MDR strains were confirmed in experimentally-infected mice and rabbits, using dynamic PET with chemically identical antibiotic radioanalogs, and postmortem mass spectrometry measurements. PET-facilitated pharmacokinetic modeling predicted human dosing necessary to attain therapeutic brain exposures in human subjects. These data were used to design optimized, pretomanid-based regimens which were evaluated at human equipotent dosing in a mouse model of TB meningitis, demonstrating excellent bactericidal activity without an increase in intracerebral inflammation or brain injury. Importantly, several antibiotic regimens demonstrated discordant activities in brain and lung tissues in the same animal, correlating with the compartmentalized tissue exposures of the component antibiotics. These data provide a mechanistic basis for the compartmentalized activities of antibiotic regimens, with important implications for the development of antimicrobial regimens for meningitis and other infections in compartments with unique antibiotic penetration.

7.
Curr Alzheimer Res ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38623983

ABSTRACT

Alzheimer's disease [AD] is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and functional impairment. Despite extensive research, the exact etiology remains elusive. This review explores the multifaceted pathophysiology of AD, focusing on key hypotheses such as the cholinergic hypothesis, hyperphosphorylated Tau Protein and Amyloid ß hypothesis, oxidative stress hypothesis, and the metal ion hypothesis. Understanding these mechanisms is crucial for developing effective therapeutic strategies. Current treatment options for AD have limitations, prompting the exploration of alternative approaches, including herbal interventions. Cholinesterase inhibitors, targeting the cholinergic hypothesis, have shown modest efficacy in managing symptoms. Blocking Amyloid ß [Aß] and targeting hyperphosphorylated tau protein are under investigation, with limited success in clinical trials. Oxidative stress, implicated in AD pathology, has led to the investigation of antioxidants. Natural products, such as Punica granatum Linn, Radix Scutellariae, and Curcuma longa have demonstrated antioxidant properties, along with anti-inflammatory effects, offering potential neuroprotective benefits. Several herbal extracts, including Ginkgo biloba, Bacopa monnieri, and Withania somnifera, have shown promise in preclinical studies. Compounds like Huperzine A, Melatonin, and Bryostatin exhibit neuroprotective effects through various mechanisms, including cholinergic modulation and anti-inflammatory properties. However, the use of herbal drugs for AD management faces limitations, including standardization issues, variable bioavailability, and potential interactions with conventional medications. Additionally, the efficacy and safety of many herbal products remain to be established through rigorous clinical trials. This review also highlights promising natural products currently in clinical trials, such as Resveratrol and Homotaurine, and their potential impact on AD progression. DHA, an omega-3 fatty acid, has shown cognitive benefits, while Nicotine is being explored for its neuroprotective effects. In conclusion, a comprehensive understanding of the complex pathophysiology of AD and the exploration of herbal interventions offer a holistic approach to managing this devastating disease. Future research should address the limitations associated with herbal drugs and further evaluate the efficacy of promising natural products in clinical settings.

8.
bioRxiv ; 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38617362

ABSTRACT

Many data resources generate, process, store, or provide kidney related molecular, pathological, and clinical data. Reference ontologies offer an opportunity to support knowledge and data integration. The Kidney Precision Medicine Project (KPMP) team contributed to the representation and addition of 329 kidney phenotype terms to the Human Phenotype Ontology (HPO), and identified many subcategories of acute kidney injury (AKI) or chronic kidney disease (CKD). The Kidney Tissue Atlas Ontology (KTAO) imports and integrates kidney-related terms from existing ontologies (e.g., HPO, CL, and Uberon) and represents 259 kidney-related biomarkers. We also developed a precision medicine metadata ontology (PMMO) to integrate 50 variables from KPMP and CZ CellxGene data resources and applied PMMO for integrative kidney data analysis. The gene expression profiles of kidney gene biomarkers were specifically analyzed under healthy control or AKI/CKD disease statuses. This work demonstrates how ontology-based approaches support multi-domain data and knowledge integration in precision medicine.

9.
Clin Infect Dis ; 78(5): 1148-1153, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38441140

ABSTRACT

Fever of unknown origin (FUO) is a clinical conundrum for patients and clinicians alike, and imaging studies are often performed as part of the diagnostic workup of these patients. Recently, the Society of Nuclear Medicine and Molecular Imaging convened and approved a guideline on the use of nuclear medicine tools for FUO. The guidelines support the use of 2-18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in adults and children with FUO. 18F-FDG PET/CT allows detection and localization of foci of hypermetabolic lesions with high sensitivity because of the 18F-FDG uptake in glycolytically active cells that may represent inflammation, infection, or neoplasia. Clinicians should consider and insurers should cover 18F-FDG PET/CT when evaluating patients with FUO, particularly when other clinical clues and preliminary studies are unrevealing.


Subject(s)
Fever of Unknown Origin , Fluorodeoxyglucose F18 , Nuclear Medicine , Positron Emission Tomography Computed Tomography , Humans , Fever of Unknown Origin/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Nuclear Medicine/methods , Adult , Radiopharmaceuticals , Child , Practice Guidelines as Topic
10.
Nat Commun ; 15(1): 2511, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38509069

ABSTRACT

In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. There has been a surge of multiplexed RNA in situ mapping techniques but their application to human tissues has been limited due to their large size, general lower tissue quality and high autofluorescence. Here we report DART-FISH, a padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections. We introduce an omni-cell type cytoplasmic stain that substantially improves the segmentation of cell bodies. Our enzyme-free isothermal decoding procedure allows us to image 121 genes in large sections from the human neocortex in <10 h. We successfully recapitulated the cytoarchitecture of 20 neuronal and non-neuronal subclasses. We further performed in situ mapping of 300 genes on a diseased human kidney, profiled >20 healthy and pathological cell states, and identified diseased niches enriched in transcriptionally altered epithelial cells and myofibroblasts.


Subject(s)
Gene Expression Profiling , RNA , Humans , RNA/genetics , In Situ Hybridization , Gene Expression Profiling/methods , Transcriptome , Cytosol
12.
bioRxiv ; 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38464264

ABSTRACT

Chronic kidney disease (CKD) is associated with renal metabolic disturbances, including impaired fatty acid oxidation (FAO). Nicotinamide adenine dinucleotide (NAD + ) is a small molecule that participates in hundreds of metabolism-related reactions. NAD + levels are decreased in CKD, and NAD + supplementation is protective. However, both the mechanism of how NAD + supplementation protects from CKD, as well as the cell types most responsible, are poorly understood. Using a mouse model of Alport syndrome, we show that nicotinamide riboside (NR), an NAD + precursor, stimulates renal peroxisome proliferator-activated receptor α signaling and restores FAO in the proximal tubules, thereby protecting from CKD in both sexes. Bulk RNA-sequencing shows that renal metabolic pathways are impaired in Alport mice and dramatically activated by NR in both sexes. These transcriptional changes are confirmed by orthogonal imaging techniques and biochemical assays. Single nuclei RNA-sequencing and spatial transcriptomics, both the first of their kind from Alport mice, show that NAD + supplementation restores FAO in the proximal tubules with minimal effects on the podocytes. Finally, we also report, for the first time, sex differences at the transcriptional level in this Alport model. Male Alport mice had more severe inflammation and fibrosis than female mice at the transcriptional level. In summary, the data herein identify both the protective mechanism and location of NAD + supplementation in this model of CKD.

13.
Curr Pharm Des ; 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38477208

ABSTRACT

Cardiovascular Disease (CVD) is one of the most prevalent diseases in the world, comprising a variety of disorders such as hypertension, heart attacks, Peripheral Vascular Disease (PVD), dyslipidemias, strokes, coronary heart disease, and cardiomyopathies. The World Health Organization (WHO) predicts that 22.2 million people will die from CVD in 2030. Conventional treatments for CVDs are often quite expensive and also have several side effects. This potentiates the use of medicinal plants, which are still a viable alternative therapy for a number of diseases, including CVD. Natural products' cardio-protective effects result from their anti-oxidative, anti-hypercholesterolemia, anti-ischemic, and platelet aggregation-inhibiting properties. The conventional therapies used to treat CVD have the potential to be explored in light of the recent increase in the popularity of natural goods and alternative medicine. Some natural products with potential in the management of cardiovascular diseases such as Allium sativum L., Ginkgo biloba, Cinchona ledgeriana, Ginseng, Commiphora mukul, Digitalis lanata, Digitalis purpurea L., Murrayakoenigii, Glycyrrhiza glabra, Polygonum cuspidatum, Fenugreek, Capsicum annuum, etc. are discussed in this article.

14.
Nat Commun ; 15(1): 1599, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38383552

ABSTRACT

Lipids play crucial roles in many biological processes. Mapping spatial distributions and examining the metabolic dynamics of different lipid subtypes in cells and tissues are critical to better understanding their roles in aging and diseases. Commonly used imaging methods (such as mass spectrometry-based, fluorescence labeling, conventional optical imaging) can disrupt the native environment of cells/tissues, have limited spatial or spectral resolution, or cannot distinguish different lipid subtypes. Here we present a hyperspectral imaging platform that integrates a Penalized Reference Matching algorithm with Stimulated Raman Scattering (PRM-SRS) microscopy. Using this platform, we visualize and identify high density lipoprotein particles in human kidney, a high cholesterol to phosphatidylethanolamine ratio inside granule cells of mouse hippocampus, and subcellular distributions of sphingosine and cardiolipin in human brain. Our PRM-SRS displays unique advantages of enhanced chemical specificity, subcellular resolution, and fast data processing in distinguishing lipid subtypes in different organs and species.


Subject(s)
Microscopy , Nonlinear Optical Microscopy , Animals , Mice , Humans , Nonlinear Optical Microscopy/methods , Spectrum Analysis, Raman/methods , Lipids
15.
Clin Exp Rheumatol ; 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38372731

ABSTRACT

OBJECTIVES: GMCSF+T-cells may be involved in pathogenesis of rheumatoid arthritis (RA), and polyfunctionality may be a marker of pathogenicity. Although, higher frequencies of CD4+GMCSF+ T-cells have been reported, there are no data on CD8+GMCSF+ T-cells or polyfunctionality.Our objective was to enumerate frequencies of CD8+GMCSF+ T cells in RA blood and synovial fluid (SF), and assess their polyfunctionality, memory phenotype and cytotoxic ability. METHODS: This study included RA patients (blood samples,in some with paired synovial fluid (SF)), healthy controls (HC) (blood) and SpA patients (SF). In some RA patients' blood was sampled twice, before and 16-24 weeks after methotrexate (MTX) treatment. After mononuclear cell isolation from blood and SF, ex-vivo stimulation using PMA/Ionomycin was done, and cells were stained (surface and intracellular after permeabilisation/fixation). Subsequently, frequencies of GMCSF+CD8+ and CD4+ T-cells, polyfunctionality (TNFα, IFNγ, IL-17), phenotype (memory) and perforin/granzyme expression were assessed by flowcytometry. RESULTS: There was no significant difference in frequencies of GMCSF+CD8+ (3.7, 4.1%, p=0.540) or GMCSF+CD4+ T-cells (4.5, 5.2%, p=0.450) inblood of RA and HC. However, there was significant enrichment of both CD8+GMCSF+ (5.8, 3.9%, p=0.0045) and CD4+GMCSF+ (8.5, 4.5%, p=0.0008) T-cells inSF compared to blood in RA patients. Polyfunctional triple cytokine positive TNFα+IFNγ+GMCSF+CD8+T-cells (81, 36%, p=0.049) and CD4+T-cells (48, 32%, p=0.010) was also higher in SF compared to blood in RA. CD8+ T cells showed higher frequency of effector-memory phenotype and granzyme-B expression in RA-SF. On longitudinal follow-up, blood CD4+GMCSF+ T-cells significantly declined (4.6, 2.9%, p=0.0014) post-MTX. CONCLUSIONS: We report a novel finding of enrichment of CD8+GMCSF+ in addition to CD4+GMCSF+ T-cells in RA-SF. These cells showed higher polyfunctionality for TNFα and IFNγ, and effector memory phenotype suggesting their involvement in RA pathogenesis.

16.
Nat Commun ; 15(1): 433, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38199997

ABSTRACT

There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidney's active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we note distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3, KLF6, and KLF10 regulates the transition between health and injury, while in thick ascending limb cells this transition is regulated by NR2F1. Further, combined perturbation of ELF3, KLF6, and KLF10 distinguishes two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks.


Subject(s)
Chromatin , Kidney , Humans , Chromatin/genetics , Kidney Tubules, Proximal , Health Status , Cell Count
17.
Article in English | MEDLINE | ID: mdl-38199059

ABSTRACT

Arbortristoside-A (Arbor-A) is a naturally occurring iridoid glycoside and herbal-based lead molecule with proven medicinal potential. Aiming at the development of an efficient analytical tool for the quantification of Arbor-A in pharmaceutical dosage forms, in the presented work, we developed an economical, fast, and sensitive RP-HPLC-UV method and validated the procedure as per the ICH guidelines, Q2(R1). The chromatographic separation was accomplished under the optimised experimental conditions using an HPLC system with an LC-2010 autosampler, a PDA detector, and a Phenomenex C18 column with the mobile phase composed of a 70:30 (v/v) water-acetonitrile mixture eluting isocratically at a flow rate of 1 mL/min at ambient temperature, and UV detection at 310 nm. Arbor-A showed a sharp peak at the retention time of 5.60 min and exhibited linearity (R2 = 0.9988) with LOD and LOQ of 0.50 µg/mL and 1.50 µg/mL, respectively. The accuracy of the method was 98.33-101.36 % with acceptable intra-day and inter-day precisions as well as robustness (<2% RSD). To ratify the applicability of the presented approach in emerging pharmaceuticals, a nanoformulation loaded with Arbor-A was designed and analysed utilising the provided methodology. The method has also enabled to determine the degradation kinetics of Arbor-A under stress conditions, etcetera, employing forced degradation and short term stability studies.


Subject(s)
Chromatography, High Pressure Liquid , Iridoid Glucosides , Chromatography, High Pressure Liquid/methods , Limit of Detection , Drug Stability , Reproducibility of Results , Pharmaceutical Preparations
18.
Curr Drug Targets ; 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38213164

ABSTRACT

BACKGROUND: Tablet formulation could be revolutionized by the integration of modern technology and established pharmaceutical sciences. The pharmaceutical sector can develop tablet formulations that are not only more efficient and stable but also patient-friendly by utilizing artificial intelligence (AI), machine learning (ML), and materials science. OBJECTIVES: The primary objective of this review is to explore the advancements in tablet technology, focusing on the integration of modern technologies like artificial intelligence (AI), machine learning (ML), and materials science to enhance the efficiency, cost-effectiveness, and quality of tablet formulation processes. METHODS: This review delves into the utilization of AI and ML techniques within pharmaceutical research and development. The review also discusses various ML methodologies employed, including artificial neural networks, an ensemble of regression trees, support vector machines, and multivariate data analysis techniques. RESULTS: Recent studies showcased in this review demonstrate the feasibility and effectiveness of ML approaches in pharmaceutical research. The application of AI and ML in pharmaceutical research has shown promising results, offering a potential avenue for significant improvements in the product development process. CONCLUSION: The integration of nanotechnology, AI, ML, and materials science with traditional pharmaceutical sciences presents a remarkable opportunity for enhancing tablet formulation processes. This review collectively underscores the transformative role that AI and ML can play in advancing pharmaceutical research and development, ultimately leading to more efficient, reliable and patient-centric tablet formulations.

19.
Indian J Orthop ; 58(1): 79-88, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38161394

ABSTRACT

Background: Distal biceps tears are uncommon injuries, typically leading to significant loss of elbow flexion and supination strength; surgical repairs restore muscular strength and endurance. The aim of this study was to compare the complication rate of early (< 21 days) vs delayed (> 21 days) repair and the effect of types of incision and fixation methods used in the repair. Methods: A total of 86 cases were retrospectively reviewed, and 66 cases were included in the study after exclusion. Different preoperative and intraoperative variables and postoperative outcome measures were recorded. We analysed the effects of early and delayed repair, types of incision and fixation methods on the complications. Results: 31 had an early, and 35 had delayed distal biceps repair. The mean follow-up was 14.92 weeks. 13.6% had major, and 40.9% had minor complications. No significant difference was noted in complications between the two groups (54.8% vs 54.3%). Higher complications were observed when surgery was done using a single anterior incision compared to 2 anterior incisions (68.8% vs 16.7%, p=0.0002). Overall, higher (76.3% vs 25.9%, p=0.0001) complications were noted in patients where fixation was done using a cortical button & interference screw in comparison to the cortical button alone. Conclusion: No significant difference in complication was noted between early and delayed repair. However, more complications were noted in the single anterior incision compared to the two anterior incision technique. Higher complications were also observed with the cortical button and interference screw fixation method compared to the cortical button alone.

20.
Curr Rheumatol Rev ; 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38284718

ABSTRACT

BACKGROUND: Guggulipid, an oleo-gum resin extracted from the bark of Commiphora wightii of the Burseraceae family, holds a significant place in Ayurvedic medicine due to its historical use in treating various disorders, including inflammation, gout, rheumatism, obesity, and lipid metabolism imbalances. OBJECTIVE: This comprehensive review aims to elucidate the molecular targets of guggulipids and explore their cellular responses. Furthermore, it summarizes the findings from in-vitro, in-vivo, and clinical investigations related to arthritis and various inflammatory conditions. METHODS: A comprehensive survey encompassing in-vitro, in-vivo, and clinical studies has been conducted to explore the therapeutic capacity of guggulipid in the management of rheumatoid arthritis. Various molecular pathways, such as cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), PI3-kinase/AKT, JAK/STAT, nitric oxide synthase (iNOS), and NFκB signaling pathways, have been targeted to assess the antiarthritic and anti-inflammatory effects of this compound. RESULTS: The research findings reveal that guggulipid demonstrates notable antiarthritic and anti-inflammatory effects by targeting key molecular pathways involved in inflammatory responses. These pathways include COX-2, VEGF, PI3-kinase/AKT, JAK/STAT, iNOS, and NFκB signaling pathways. in-vitro, in-vivo, and clinical studies collectively support the therapeutic potential of guggulipid in managing rheumatoid arthritis and related inflammatory conditions. CONCLUSION: This review provides a deeper understanding of the therapeutic mechanisms and potential of guggulipid in the management of rheumatoid arthritis. The collective evidence strongly supports the promising role of guggulipid as a therapeutic agent, encouraging further research and development in guggulipid-based treatments for these conditions.

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