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2.
Cell Death Dis ; 15(5): 331, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740775

ABSTRACT

Pirh2 is an E3 ubiquitin ligase known to regulate the DNA damage responses through ubiquitylation of various participating signaling factors. DNA damage is a key pathological contributor to Alzheimer's disease (AD), therefore, the role of Pirh2 was investigated in streptozotocin and oligomer Aß1-42 induced rodent experimental model of AD. Pirh2 protein abundance increased during AD conditions, and transient silencing of Pirh2 inhibited the disease-specific pathological markers like level of p-Tau, ßamyloid, acetylcholinesterase activity, and neuronal death. Biochemically, Pirh2 silencing significantly attenuated the oxidative stress, depleted mitochondrial membrane potential, cytochrome c translocation from mitochondria to cytosol, and depleted mitochondrial complex-I activity, and ATP level. Pirh2 silencing also inhibited the altered level of VDAC1, hsp75, hexokinase1, t-Bid, caspase-9, and altered level of apoptotic proteins (Bcl-2, Bax). MALDI-TOF/TOF, co-immunoprecipitation, and UbcH13-linked ubiquitylation assay confirmed the interaction of Pirh2 with cytochrome c and the role of Pirh2 in ubiquitylation of cytochrome c, along with Pirh2-dependent altered proteasome activity. Additionally, Pirh2 silencing further inhibited the translocation of mitochondrion-specific endonuclease G and apoptosis-inducing factors to the nucleus and DNA damage. In conclusion, findings suggested the significant implication of Pirh2 in disease pathogenesis, particularly through impaired mitochondrial function, including biochemical alterations, translocation of cytochrome c, endonuclease G and apoptosis-inducing factor, DNA damage, and neuronal apoptosis.


Subject(s)
Alzheimer Disease , Cytochromes c , Mitochondria , Neurons , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Alzheimer Disease/genetics , Animals , Cytochromes c/metabolism , Mitochondria/metabolism , Neurons/metabolism , Neurons/pathology , Oxidative Stress , Rats , Male , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Amyloid beta-Peptides/metabolism , Membrane Potential, Mitochondrial , Ubiquitination , Humans , Apoptosis , Cell Death , Rats, Sprague-Dawley , Disease Models, Animal , Endodeoxyribonucleases
3.
Sci Rep ; 14(1): 10035, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693147

ABSTRACT

In the fast-paced fashion world, unique designs are like early birds, grabbing attention as online shopping surges. Fabric texture plays an immense role in selecting the perfect design. Indian Traditional textile motifs are pivotal, showing rich cultural origins and attracting worldwide art fanatics. Yet, technology-driven abstract forms are posing a challenge for them. The decline of handmade artistic ability due to computerization is concerning. Crafting new designs associated with the latest trends is time- consuming and requires diligence. In this work an interactive CBIR (content-based image retrieval) system is presented. It utilizes deep features from InceptionV3 and InceptionResNetV2 models to match query designs with a database of traditional Indian textiles. Its performance is tested with Caltech-101, Corel-1K state-of-the-art datasets, and Indian Textiles datasets and the results are shown to be finer than the existing approaches. The similarity-based fine-grained saliency maps (SBFGSM) approach is employed to visualize the importance of features. Our approach combines deep feature fusion with PCA dimensionality reduction and speeds up search using a clustering approach. Relevance feedback is employed to refine the retrievals. This tool is expected to benefit designers by accelerating the design cycles by bridging the gap between human creativity and A.I. assistance.

4.
Gene ; 920: 148526, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-38703866

ABSTRACT

INTRODUCTION: Outer membrane protein (OMP) of Helicobacter pylori (H. pylori) i.e., blood group antigen binding adhesin (babA) is responsible for the attachment of H. pylori in the gastric epithelium. Its adherence is causative for gastric pathology such as gastritis, peptic ulcer disease (PUD), or digestive tract disorders like erosive reflux disease (ERD) and (NERD) non-erosive reflux disease and together called Gastroesophageal reflux disease (GERD). BabA manifests rapid and varied selection via substitution of amino acid in its Leb-carbohydrate binding domain (CBD) which enables better binding preferences for distinct human populations and ABO blood group phenotypes. The positive evolutionary selection of the pathogenic factor of this genetically diverse bacterium has enabled it to adapt to the host gastric environment. Analyzing the association of virulent genes (cagA, vacA) and babA will help us better understand bacteria's pathogenicity. METHOD: 109 H. pylori strains from patients with distinct gastrointestinal diseases were genotyped using Polymerase Chain Reaction(PCR) for cagA, vacA, and babA followed by Sanger sequencing and phylogenetic analysis. RESULT: In the babA + ve genotype, a statistically significant association with p = 0.04 and < 0.0001 is seen in gastritis and ERD respectively. A significant association of genotype vacAs1m2 (p = 0.0002) was seen in gastritis, vacAs1m1 (p = 0.02) in NERD, vacAs1m1 (p < 0.0001) and vacAs1m2 (p = 0.002) in ERD. This relationship helps to detect gastritis or ERD where BabA gene can be used as an independent marker for detecting their presence. CONCLUSION: The appearance of variants within distinct disease categories is due to local genetic variation.


Subject(s)
Adhesins, Bacterial , Helicobacter Infections , Helicobacter pylori , Phylogeny , Humans , Helicobacter pylori/genetics , Helicobacter pylori/pathogenicity , Helicobacter pylori/isolation & purification , Adhesins, Bacterial/genetics , Helicobacter Infections/microbiology , India , Male , Gastritis/microbiology , Female , Gastrointestinal Diseases/microbiology , Gastrointestinal Diseases/genetics , Antigens, Bacterial/genetics , Genotype , Adult , Middle Aged , Bacterial Proteins/genetics
5.
J Microsc Ultrastruct ; 12(1): 43-45, 2024.
Article in English | MEDLINE | ID: mdl-38633573

ABSTRACT

Although myopericytoma and glomangiopericytoma are considered the subtypes of the group myopericytomas (MPC), they differ morphologically. Both of the tumors arise from pericytic cells. Scalp MPC are infrequent, but extranasal glomangiopericytomas are extremely rare. Herein, we report a case of a 36-year-old female presenting with slowly growing scalp swelling. Histopathology showed a dermal tumor with features of myopericytoma as well as glomangiopericytoma within the same lesion. Immunohistochemistry and reticulin staining confirmed pericytic origin but could not differentiate between the two tumors. This case report adds to the rarity and morphologic heterogeneity of the group MPC.

6.
Front Plant Sci ; 15: 1335965, 2024.
Article in English | MEDLINE | ID: mdl-38384769

ABSTRACT

Ocimum tenuiflorum, commonly known as "Holy basil," is renowned for its notable medicinal and aromatic attributes. Its unique fragrance attributes to specific volatile phytochemicals, primarily belonging to terpenoid and/or phenylpropanoid classes, found within their essential oils. The use of nanoparticles (NPs) in agriculture has attracted attention among plant researchers. However, the impact of NPs on the modulation of morpho-physiological aspects and essential oil production in medicinal plants has received limited attention. Consequently, the present study aimed to explore the effect of silicon dioxide (SiO2) and titanium dioxide (TiO2) nanoparticles at various concentrations (viz., DDW (control), Si50+Ti50, Si100+Ti50, Si100+Ti100, Si200+Ti100, Si100+Ti200 and Si200+Ti200 mg L-1) on growth, physiology and essential oil production of O. tenuiflorum at 120 days after planting (DAP). The results demonstrated that the combined application of Si and Ti (Si100+Ti100 mg L-1) exhibited the most favourable outcomes compared to the other combinational treatments. This optimal treatment significantly increased the vegetative growth parameters (root length (33.5%), shoot length (39.2%), fresh weight (62.7%) and dry weight (28.5%)), photosynthetic parameters, enzymatic activities (nitrate reductase and carbonic anhydrase), the overall area of PGTs (peltate glandular trichomes) and essential oil content (172.4%) and yield (323.1%), compared to the control plants. Furthermore, the GCMS analysis showed optimal treatment (Si100+Ti100) significantly improved the content (43.3%) and yield (151.3%) of eugenol, the primary active component of the essential oil. This study uncovers a remarkable and optimal combination of SiO2 and TiO2 nanoparticles that effectively enhances the growth, physiology, and essential oil production in Holy basil. These findings offer valuable insights into maximizing the potential benefits of its use in industrial applications.

7.
Tuberculosis (Edinb) ; 145: 102479, 2024 03.
Article in English | MEDLINE | ID: mdl-38262199

ABSTRACT

Persistence of Mycobacterium tuberculosis (Mtb) is one of the challenges to successful treatment of tuberculosis (TB). In vitro models of non-replicating Mtb are used to test the efficacy of new molecules against Mtb persisters. The H37Ra strain is attenuated for growth in macrophages and mice. We validated H37Ra-infected immunocompetent mice for testing anti-TB molecules against slow/non-replicating Mtb in vivo. Swiss mice were infected intravenously with H37Ra and monitored for CFU burden and histopathology for a period of 12 weeks. The bacteria multiplied at a slow pace reaching a maximum load of ∼106 in 8-12 weeks depending on the infection dose, accompanied by time and dose-dependent histopathological changes in the lungs. Surprisingly, four-weeks of treatment with isoniazid-rifampicin-ethambutol-pyrazinamide combination caused only 0.4 log10 and 1 log10 reduction in CFUs in lungs and spleen respectively. The results show that ∼40 % of the H37Ra bacilli in lungs are persisters after 4 weeks of anti-TB therapy. Isoniazid/rifampicin monotherapy also showed similar results. A combination of bedaquiline and isoniazid reduced the CFU counts to <200 (limit of detection), compared to ∼5000 CFUs by isoniazid alone. The study demonstrates an in vivo model of Mtb persisters for testing new leads using a BSL-2 strain.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Animals , Mice , Isoniazid/pharmacology , Isoniazid/therapeutic use , Rifampin/pharmacology , Rifampin/therapeutic use , Tuberculosis/drug therapy , Tuberculosis/microbiology , Pyrazinamide/therapeutic use , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use
8.
Heliyon ; 9(11): e21646, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38058652

ABSTRACT

Nanoparticles (NPs) have gained considerable interest among researchers in the field of plant biology, particularly in the agricultural sector. Among the numerous NPs, the individual application of silicon (Si) or titanium (Ti), in their oxide forms, had a positive influence on growth, physiochemical and yield attributes of plants. However, the synergetic application of both these NPs has not been studied yet. Therefore, the current study was aimed to investigate the effect of combined application of silicon dioxide (SiO2) and titanium dioxide (TiO2) NPs on the growth characters, physiological parameters, and essential oil quality and production of Coleus aromatics Benth. Aqueous solutions of nanoparticles were applied to the foliage of the plants at varying combinations (Si50+Ti50, Si100+Ti50, Si100+Ti100, Si200+Ti100, Si100+Ti200 and Si200+Ti200 mg L-1). Various morpho-physiological, biochemical and yield attributes were assessed at 120 days after planting. The results demonstrated that both Si and Ti NPs improved the growth and photosynthetic efficiency in a dose dependent manner. The best results were obtained by the combined application of Si100+Ti100 mg L-1, and thereafter, the values declined progressively. The maximum improvement in fresh weight (39.5 %) and dry weight (40.8 %) of shoot, fresh weight (45.7 %) and dry weight (49.4 %) of root was observed as compared to respective controls. Moreover, the exogenous application of Si100+Ti100 mg L-1 increased photosynthetic attributes such as total content of chlorophyll (41.7 %), carotenoids (43.7 %), chlorophyll fluorescence (7.1 %), and carbonic anhydrase (23.8 %). All of these contributed to the highest accumulation in the content (129.0 %) and yield (215.5 %) of essential oil (EO), in comparison to the control. Thus, results encouraged the use of SiO2 and TiO2 NPs to be applied in combined form to boost the essential oil production of Coleus aromaticus. The findings of this study may serve agronomists to determine the optimal concentrations of NPs for enhanced production of bioactive compounds with a wide range of industrial applications.

9.
Indian J Pathol Microbiol ; 66(4): 758-763, 2023.
Article in English | MEDLINE | ID: mdl-38084528

ABSTRACT

Background: As the world has been going through a pandemic of coronavirus disease 2019 (COVID-19) for the past two years, a safe and effective vaccine was urgently needed. Vaccination against the disease was launched in India on January 16, 2021 with healthcare workers, frontline workers, and the elderly above 60 years being the first beneficiaries. Vaccines being used in India are Covishield and Covaxin. Materials and Methods: Fifteen healthcare workers (HCWs) who were vaccinated with Covishield or Covaxin were included in the study, and T cell, B cell and antibody response of the HCWs were analyzed. Blood samples collected from every subject were sent for antibody analysis, hematological workup for cell counts, and flow cytometry was performed for various subsets of lymphocytes. Hematological variables in naïve HCWs (who never had any natural infection) and recovered HCWs (those recovered from natural infection) were compared. Results: Antibody index among recovered HCWs was significantly higher than the naïve HCWs. All the leucocyte parameters showed a higher median value in the recovered group except total leucocyte count (TLC), T helper cell count (Th cell), T helper cell to T cytotoxic cell (Th cell: CTL) ratio and natural killer (NK) cell. But only Th: CTL ratio showed a statistically significant difference. Conclusion: This study shows that the antibody index among individuals who had both vaccination and COVID-19 infection is significantly higher than those who just had vaccination. T helper cell to T cytotoxic cell ratio is lowered in the recovered HCWs as compared to the naïve HCWs and this finding is statistically significant.


Subject(s)
COVID-19 , ChAdOx1 nCoV-19 , Aged , Humans , COVID-19 Vaccines , COVID-19/prevention & control , Vaccination , Antibodies , Health Personnel , Leukocyte Count , Immunity
10.
J Cell Physiol ; 238(12): 2841-2854, 2023 12.
Article in English | MEDLINE | ID: mdl-37882235

ABSTRACT

Amyloid-ß (Aß) protein aggregation in the brain is a pathological hallmark of Alzheimer's disease (AD) however, the underlying molecular mechanisms regulating amyloid aggregation are not well understood. Here, we studied the propitious role of E3 ubiquitin ligase Pirh2 in Aß protein aggregation in view of its regulatory ligase activity in the ubiquitin-proteasome system employing both cellular and sporadic rodent models of AD. Pirh2 protein abundance was significantly increased during Streptozotocin (STZ) induced AD conditions, and transient silencing of Pirh2 significantly inhibited the Aß aggregation and modified the dendrite morphology along with the substantial decrease in choline level in the differentiated neurons. MALDI-TOF/TOF, coimmunoprecipitation, and UbcH7-linked in vitro ubiquitylation analysis confirmed the high interaction of Pirh2 with chaperone GRP78. Furthermore, Pirh2 silencing inhibits the STZ induced altered level of endoplasmic reticulum stress and intracellular Ca2+ levels in neuronal N2a cells. Pirh2 silencing also inhibited the AD conditions related to the altered protein abundance of HSP90 and its co-chaperones which may collectively involve in the reduced burden of amyloid aggregates in neuronal cells. Pirh2 silencing further stabilized the nuclear translocation of phospho-Nrf2 and inhibited the altered level of autophagy factors. Taken together, our data indicated that Pirh2 is critically involved in STZ induced AD pathogenesis through its interaction with ER-chaperone GRP78, improves the neuronal connectivity, affects the altered level of chaperones, co-chaperones, & autophagic markers, and collectively inhibits the Aß aggregation.


Subject(s)
Alzheimer Disease , Endoplasmic Reticulum Chaperone BiP , Signal Transduction , Alzheimer Disease/pathology , Amyloid , Amyloid beta-Peptides/metabolism , Glucose/metabolism , Molecular Chaperones/genetics , Molecular Chaperones/metabolism , Protein Aggregates , Male , Animals , Mice , Rats , Cell Line, Tumor , Rats, Sprague-Dawley , Endoplasmic Reticulum Stress
11.
J Phys Chem Lett ; 14(42): 9479-9489, 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37831811

ABSTRACT

The critical photophysical properties of lead-free halide double perovskites (HDPs) must be substantially improved for various applications. In this regard, strain engineering is a powerful tool for enhancing optoelectronic performance with precise control. Here, we employ ab initio simulations to investigate the impact of mild compressive and tensile strains on the photophysics of Cs2AgB'X6 (B' = Sb, Bi; X = Cl, Br) perovskites. Depending on the pnictogen and halide atoms, the band gap and band edge positions of HDPs can be tuned to a significant extent by controlling the applied external strain. Cs2AgSbBr6 has the most substantial strain response under structural perturbations. The subtle electronic interactions among the participating orbitals and the band dispersion at the edge states are enhanced under compressive strain, reducing the carrier effective masses. The exciton binding energies for these Br-based HDPs are in the range 59-78 meV and weaken in the compressed lattices, suggesting improved free carrier generation. Overall, the study emphasizes the potential of lattice strain engineering to boost the photophysical properties of HDPs that can ultimately improve their optoelectronic performance.

14.
Int J Health Sci (Qassim) ; 17(4): 44-53, 2023.
Article in English | MEDLINE | ID: mdl-37416843

ABSTRACT

Objective: In today's global clinical settings, low-field magnetic resonance imaging (MRI) technology is becoming increasingly prevalent. Ensuring high-quality image acquisition is crucial for accurate disease diagnosis and treatment and for evaluating the impact of poor-quality images. In this study, we explored the potential of deep learning as a diagnostic tool for improving image quality in hydrocephalus analysis planning. This could include discussions on the diagnostic accuracy, cost-effectiveness, and practicality of using low-field MRI as an alternative. Methods: There are many reasons which are going to affect infant computed tomography images. These are spatial resolution, noise, and contrast between the brain and cerebrospinal fluid (CSF). Now, we can enhance using the application of deep learning algorithms. Both improved and down quality were situated to the three qualified pediatric neurosurgeons comfortable with working in poor- to middle-level income countries for the analysis of clinical tools in the planning of the treatment of hydrocephalus. Results: The results predict that a picture will be classified as beneficial for hydrocephalus treatment planning, according to image resolution and the contrast-to-noise ratio (CNR) between the brain and CSF. The CNR is significantly improved by deep learning enhancement, which also improves the apparent likelihood of the image. Conclusion: However, poor-quality images might be desirable to image improved by deep learning, since those images will not offer the risk of confusing facts which could misguide the decision of the analysis of patients. Such findings support the newly introduced measurement standards in estimating the acceptable quality of images for clinical use.

15.
Front Plant Sci ; 14: 1129130, 2023.
Article in English | MEDLINE | ID: mdl-37152142

ABSTRACT

Introduction: The current study was carried out with the hypothesis that foliar application of plant-derived smoke water (PDSW) and karrikinolide (KAR1) might enhanced the plant growth, physiology, and essential oil production of the Mentha arvensis L. Karrikinolide (KAR1) is one of the most important bioactive constituents of PDSW. Methods: Mint (Mentha arvensis L.) was grown in natural conditions in the net-house. Different concentrations of PDSW (1:125, 1:250, 1:500 and 1:1000 v/v) and KAR1 (10-9 M, 10-8 M, 10-7 M and 10-6 M) were used as foliar-spray treatments, using double-distilled water as control. The PDSW was prepared by burning the dried wheat-straw that acted as a growth-promoting substance. Results: Foliar-spray treatment 1:500 v/v of PDSW and 10-8 M of KAR1 proved optimal for enhancing all morphological, physiological, and essential-oil yield related parameters. In comparison with the control, 1:500 v/v of PDSW and 10-8 M of KAR1 increased significantly (p ≤ 0.05) the height of mint plant (19.23% and 16.47%), fresh weight (19.30% and 17.44%), dry weight (35.36% and 24.75%), leaf area (18.22% and 17.46%), and leaf yield per plant (28.41% and 23.74%). In addition, these treatments also significantly increased the photosynthetic parameters, including chlorophyll fluorescence (12.10% and 11.41%), total chlorophyll content (25.70% and 20.77%), and total carotenoid content (29.77% and 27.18%). Likewise, 1:500 v/v of PDSW and 10-8 M of KAR1 significantly increased the essential-oil content (37.09% and 32.25%), essential oil productivity per plant (72.22% and 66.66%), menthol content (29.94% and 25.42%), menthyl acetate content (36.90% and 31.73%), and menthone content (44.38% and 37.75%). Furthermore, the TIC chromatogram of the GCMS analysis revealed the presence of 34 compounds, 12 of which showed major peak areas. Discussion: Treatment 1: 500 v/v of PDSW proved better than the treatment 10-8 M of KAR1 with regard to most of the parameters studied. The outcome of the study can be used as a recommendation tool for agricultural and horticultural crops, since it costs much lesser than that of KAR1. In fact, the foliar application of PDSW proved economical and played bioactive role at very low concentrations.

16.
Front Cell Dev Biol ; 11: 1146564, 2023.
Article in English | MEDLINE | ID: mdl-36968195

ABSTRACT

The disturbance in mitochondrial functions and homeostasis are the major features of neuron degenerative conditions, like Parkinson's disease, Amyotrophic Lateral Sclerosis, and Alzheimer's disease, along with protein misfolding. The aberrantly folded proteins are known to link with impaired mitochondrial pathways, further contributing to disease pathogenesis. Despite their central significance, the implications of mitochondrial homeostasis disruption on other organelles and cellular processes remain insufficiently explored. Here, we have reviewed the dysfunction in mitochondrial physiology, under neuron degenerating conditions. The disease misfolded proteins impact quality control mechanisms of mitochondria, such as fission, fusion, mitophagy, and proteasomal clearance, to the detriment of neuron. The adversely affected mitochondrial functional roles, like oxidative phosphorylation, calcium homeostasis, and biomolecule synthesis as well as its axes and contacts with endoplasmic reticulum and lysosomes are also discussed. Mitochondria sense and respond to multiple cytotoxic stress to make cell adapt and survive, though chronic dysfunction leads to cell death. Mitochondria and their proteins can be candidates for biomarkers and therapeutic targets. Investigation of internetworking between mitochondria and neurodegeneration proteins can enhance our holistic understanding of such conditions and help in designing more targeted therapies.

17.
Appl Microbiol Biotechnol ; 107(7-8): 2547-2560, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36929191

ABSTRACT

The human gut is composed of diverse microflora which is influenced by dietary intake. Body mass index (BMI) and lifestyle patterns also play a vital role in human health to alter gut microbial composition. Our study aims to determine the impact of alcohol intake, BMI, and diet on gut microbiota and its relationship with gastrointestinal disorders. Thirty-nine gastric biopsies were taken from patients with various gastrointestinal (GI) diseases, and all the patient's lifestyle behavior were recorded in a written proforma. 16S rRNA metagenome analysis for V3-V4 regions was used to examine microbial compositions. The richness and diversity of gut microbiota were analyzed by PERMANOVA using the Bray-Curtis dissimilarity index and principal component analysis. The difference in relative abundance was calculated by ANOVA (p < 0.05). Alpha diversity indexes between vegetarians and non-vegetarians showed no significant difference based on BMI, alcohol status, and GI diseases. We found that in overweight vegetarian individuals Faecalibacterium and Rumicococcus might play a role in the control of Helicobacter pylori. Similarly, the increased abundance of Akkermansia muciniphila in non-vegetarian individuals with normal BMI might play a role to decrease the level of harmful bacteria like H. pylori, and Corynebacterium sp. Also, the relative abundance of Corynebacterium sp. among the vegetarians and Streptococcus sp. in the non-vegetarians was increased in alcoholics while H. pylori was increased in non-alcoholics irrespective of diet. There is an increased abundance of Faecalibacterium prausnitzii in vegetarians among all categories; however, we did not find any correlation between disease outcomes. Our study shows that alcohol intake and dietary habits have independent effects on gut microbial composition. The relative abundance of F. prausnitzii was high among vegetarians in all categories. KEY POINTS: • The presence of H. pylori is less among alcoholics. • Good bacteria help to maintain a normal body mass index. • Gut microbiota richness is high in vegetarians and diversity in non-vegetarians.


Subject(s)
Gastrointestinal Diseases , Gastrointestinal Microbiome , Humans , Gastrointestinal Microbiome/genetics , Body Mass Index , RNA, Ribosomal, 16S/genetics , Dysbiosis , Diet , Bacteria/genetics , Alcohol Drinking
18.
ACS Chem Neurosci ; 14(5): 839-850, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36755387

ABSTRACT

Mitochondrial homeostasis regulates energy metabolism, calcium buffering, cell function, and apoptosis. The present study has been conducted to investigate the implications of the ubiquitin-encoding gene UBA52 in mitochondrial physiology. Transient expression of Myc-UBA52 in neurons significantly inhibited the rotenone-induced increase in reactive oxygen species generation, nitrite level, and depleted glutathione level. Mass spectrometric and coimmunoprecipitation data suggested the profound interaction of UBA52 with mitochondrial outer membrane channel protein, VDAC1 in both the wild-type and Myc-α-synuclein overexpressed neuronal cells and in the Parkinson's disease (PD)-specific substantia nigra and striatal region of the rat brain. In vitro ubiquitylation assay revealed that UBA52 participates in the ubiquitylation of VDAC1 through E3 ligase CHIP. Myc-UBA52 overexpression in neurons further improved the mitochondrial functionality and cell viability by preventing the alteration in mitochondrial membrane potential, mitochondrial complex I activity, and translocation of cytochrome c and p-Nrf2 along with the effect on intracellular calcium uptake, thus collectively inhibiting the opening of mitochondrial permeability transition pore. Additionally, Myc-UBA52 expression in neuronal cells offered protection against apoptotic and autophagic cell death. Altogether, our findings delineate a functional association between UBA52 and mitochondrial homeostasis, providing new insights into the deterrence of dopaminergic cell death during acute PD pathogenesis.


Subject(s)
Calcium , Parkinson Disease , Animals , Rats , Apoptosis , Calcium/metabolism , Dopaminergic Neurons/metabolism , Membrane Potential, Mitochondrial , Mitochondria/metabolism , Mitochondrial Membranes/metabolism , Parkinson Disease/metabolism , Voltage-Dependent Anion Channel 1/metabolism
19.
Mol Neurobiol ; 60(5): 2397-2412, 2023 May.
Article in English | MEDLINE | ID: mdl-36656458

ABSTRACT

Cells perform regular maintenance to avoid the accumulation of misfolded proteins. Prolonged accumulation of these proteotoxic inclusions generates potential risk of ageing-related diseases such as neurodegenerative diseases. Therefore, removal of such abnormal aggregates can ensure the re-establishment of proteostasis. Ubiquitin proteasome system (UPS) actively participates in the selective removal of aberrantly folded clients with the help of complex proteasome machinery. However, specific induction of proteasome functions to remove abnormal proteins remains an open challenge. Here, we show that Itraconazole treatment induces proteasome activities and degrades the accumulation of bonafide-misfolded proteins, including heat-denatured luciferase. Exposure of Itraconazole elevates the degradation of neurodegenerative disease-associated proteins, e.g. expanded polyglutamine, mutant SOD1, and mutant α-synuclein. Our results suggest that Itraconazole treatment prevents the accumulation of neurodegenerative disease-linked misfolded proteins and generates cytoprotection. These findings reveal that Itraconazole removes abnormal proteins through sequential proteasomal activation and represents a potential protective therapeutic role against protein-misfolding neurodegenerative diseases.


Subject(s)
Neurodegenerative Diseases , Humans , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Proteasome Endopeptidase Complex/metabolism , Protein Aggregates , Itraconazole/pharmacology , Itraconazole/therapeutic use , Cytoprotection , Protein Folding
20.
Curr Microbiol ; 80(1): 35, 2022 Dec 13.
Article in English | MEDLINE | ID: mdl-36512098

ABSTRACT

Helicobacter pylori (H. pylori,) a genetically diversified bacteria which colonizes human gastric epithelium, is now established causative agent for gastric cancer worldwide. Outer membrane protein (OMP)-coding genes of H. pylori are responsible for attachment and colonization of bacteria. These genes which code proteins on outer membrane of H. pylori is a group of 33 genes which with other virulent genes are causative of giving rise to disease-causing factors in the host. OipA (Outer inflammatory protein A), a participant of Hop family of OMP, is effective in acting as a biomarker for studying progression of diseases like gastric cancer. The functionality of oipA gene is regulated by phase variation within CT repeat pattern. It is the expression, i.e., "on"/"off" of oipA gene which is related with the development of distinct gastric diseases. 40 amplified DNA sequences were studied to investigate functional status of oipA. Our results reveal 57.2% isolates with functional oipA along with significant association with cagA (P = 0.0011) and vacAs1m1/s1m2 (P = 0.0034, P = 0.0093) genotypes, respectively. In conclusion, our results indicate diversity in CT repeat pattern among Indian H. pylori strains. The prevalence of functional oipA gene was found to be ranging between 50% and 64.2% though it did not show significant correlation between functional oipA and disease outcome.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Humans , Helicobacter Infections/microbiology , Functional Status , Bacterial Outer Membrane Proteins/genetics , Bacterial Proteins/genetics , Helicobacter pylori/genetics , Antigens, Bacterial/genetics
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