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1.
Neurochem Int ; : 105761, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38723902

RESUMO

Alzheimer's disease (AD) remains one of the most formidable neurological disorders, affecting millions globally. This review provides a holistic overview of the therapeutic strategies, both conventional and novel, aimed at mitigating the impact of AD. Initially, we delve into the conventional approach, emphasizing the role of Acetylcholinesterase (AChE) inhibition, which has been a cornerstone in AD management. As our understanding of AD evolves, several novel potential approaches emerge. We discuss the promising roles of Butyrylcholinesterase (BChE) inhibition, Tau Protein inhibitors, COX-2 inhibition, PPAR-γ agonism, and FAHH inhibition, among others. The potential of the endocannabinoids (eCB) system, cholesterol-lowering drugs, metal chelators, and MMPs inhibitors are also explored, culminating in the exploration of the pivotal role of microRNA in AD progression. Parallel to these therapeutic insights, we shed light on the novel tools and methodologies revolutionizing AD research. From the quantitative analysis of gene expression by qRTPCR to the evaluation of mitochondrial function using induced pluripotent stem cells (iPSCs), the advances in diagnostic and research tools offer renewed hope. Moreover, we explore the current landscape of clinical trials, highlighting the leading drug interventions and their respective stages of development. This comprehensive review concludes with a look into the future perspectives, capturing the potential breakthroughs and innovations on the horizon. Through a synthesis of current knowledge and emerging research, this article aims to provide a consolidated resource for clinicians, researchers, and academicians in the realm of Alzheimer's disease.

2.
J Phys Condens Matter ; 36(28)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38574668

RESUMO

Flexible photodetectors (PDs) have exotic significance in recent years due to their enchanting potential in future optoelectronics. Moreover, paper-based fabricated PDs with outstanding flexibility unlock new avenues for future wearable electronics. Such PD has captured scientific interest for its efficient photoresponse properties due to the extraordinary assets like significant absorptive efficiency, surface morphology, material composition, affordability, bendability, and biodegradability. Quantum-confined materials harness the unique quantum-enhanced properties and hold immense promise for advancing both fundamental scientific understanding and practical implication. Two-dimensional (2D) materials as quantum materials have been one of the most extensively researched materials owing to their significant light absorption efficiency, increased carrier mobility, and tunable band gaps. In addition, 2D heterostructures can trap charge carriers at their interfaces, leading increase in photocurrent and photoconductivity. This review represents comprehensive discussion on recent developments in such PDs functionalized by 2D materials, highlighting charge transfer mechanism at their interface. This review thoroughly explains the mechanism behind the enhanced performance of quantum materials across a spectrum of figure of merits including external quantum efficiency, detectivity, spectral responsivity, optical gain, response time, and noise equivalent power. The present review studies the intricate mechanisms that reinforce these improvements, shedding light on the intricacies of quantum materials and their significant capabilities. Moreover, a detailed analysis of the technical applicability of paper-based PDs has been discussed with challenges and future trends, providing comprehensive insights into their practical usage in the field of future wearable and portable electronic technologies.

3.
Apoptosis ; 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38615303

RESUMO

Mycobacterium tuberculosis (Mtb) genome possesses a unique family called Proline-Glutamate/Proline-Proline-Glutamate (PE/PPE) gene family, exclusive to pathogenic mycobacterium. Some of these proteins are known to play role in virulence and immune response modulation, but many are still uncharacterized. This study investigated the role of C-terminal region of Rv1039c (PPE15) in inducing mitochondrial perturbations and macrophage apoptosis. Our in-silico studies revealed the disordered, coiled, and hydrophobic C-terminal region in Rv1039c has similarity with C-terminal of mitochondria-targeting pro-apoptotic host proteins. Wild type Rv1039c and C-terminal deleted Rv1039c (Rv1039c-/-Cterm) recombinant proteins were purified and their M. smegmatis knock-in strains were constructed which were used for in-vitro experiments. Confocal microscopy showed localization of Rv1039c to mitochondria of PMA-differentiated THP1 macrophages; and reduced mitochondrial membrane depolarization and production of mitochondrial superoxides were observed in response to Rv1039c-/-Cterm in comparison to full-length Rv1039c. The C-terminal region of Rv1039c was found to activate caspases 3, 7 and 9 along with upregulated expression of pro-apoptotic genes like Bax and Bim. Rv1039c-/-Cterm also reduced the Cytochrome-C release from the mitochondria and the expression of AnnexinV/PI positive and TUNEL positive cells as compared to Rv1039c. Additionally, Rv1039c was observed to upregulate the TLR4-NF-κB-TNF-α signalling whereas the same was downregulated in response to Rv1039c-/-Cterm. These findings suggested that the C-terminal region of Rv1039c is a molecular mimic of pro-apoptotic host proteins which induce mitochondria-dependent macrophage apoptosis and evoke host immune response. These observations enhance our understanding about the role of PE/PPE proteins at host-pathogen interface.

4.
Food Chem Toxicol ; 188: 114667, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38653447

RESUMO

Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC), associated with obesity and insulin resistance. The FDA prohibited the use of BPA-based polycarbonate resins in infant formula packaging; thus, its analogs, viz. Bisphenol S (BPS) and Bisphenol F (BPF) were considered alternatives in epoxy resins, plastics, and food cans. As these analogs might evoke a similar response, we investigated the role of Bisphenols (BPA, BPF, and BPS), on insulin signaling in CHO-HIRc-myc-GLUT4eGFP cells at environmentally relevant concentrations of 2 nM and 200 nM. Insulin signaling demonstrated that Bisphenols reduced phosphorylation of IR and AKT2, GLUT4 translocation, and glucose uptake. This was accompanied by increased oxidative stress. Furthermore, SWATH-MS-based proteomics of 3T3-L1 cells demonstrated that Bisphenol-treated cells regulate proteins in insulin resistance, adipogenesis, and fatty acid metabolism pathways differently. All three Bisphenols induced differentially expressed proteins enriched similar pathways, although their abundance differed for each Bisphenol. This might be due to their varying toxicity level, structural differences, and estrogen-mimetic activity. This study has important implications in addressing health concerns related to EDCs. Given that the analogs of BPA are considered alternatives to BPA, the findings of this study suggest they are equally potent in altering fatty acid metabolism and inducing insulin resistance.

5.
Neurosci Biobehav Rev ; 161: 105685, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38670299

RESUMO

Alzheimer's Disease (AD) remains a formidable challenge due to its complex pathology, notably involving mitochondrial dysfunction and dysregulated microRNA (miRNA) signaling. This study delves into the underexplored realm of miRNAs' impact on mitochondrial dynamics and their interplay with amyloid-beta (Aß) aggregation and tau pathology in AD. Addressing identified gaps, our research utilizes advanced molecular techniques and AD models, alongside patient miRNA profiles, to uncover miRNAs pivotal in mitochondrial regulation. We illuminate novel miRNAs influencing mitochondrial dynamics, Aß, and tau, offering insights into their mechanistic roles in AD progression. Our findings not only enhance understanding of AD's molecular underpinnings but also spotlight miRNAs as promising therapeutic targets. By elucidating miRNAs' roles in mitochondrial dysfunction and their interactions with hallmark AD pathologies, our work proposes innovative strategies for AD therapy, aiming to mitigate disease progression through targeted miRNA modulation. This contribution marks a significant step toward novel AD treatments, emphasizing the potential of miRNAs in addressing this complex disease.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , MicroRNAs , Microglia , Dinâmica Mitocondrial , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , MicroRNAs/metabolismo , MicroRNAs/genética , Humanos , Peptídeos beta-Amiloides/metabolismo , Dinâmica Mitocondrial/fisiologia , Animais , Microglia/metabolismo , Transdução de Sinais/fisiologia
6.
Autops Case Rep ; 14: e2024470, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476732

RESUMO

Lymphangiomas are rare benign tumors that mainly involve the head and neck region in pediatric patients. Lymphangiomas of the small bowel mesentery in adults are rarer. We present two cases of mesenteric lymphangioma with acute abdominal pain on presentation. Case 1: A 38-year-old female presented with abdominal pain, vomiting, fever, and difficult evacuation. On abdominal examination, she had an ill-defined, tender lump, and radiological findings raised a possibility of perforation peritonitis. Thus, exploratory laparotomy was planned. Per-operatively, a mesenteric mass was found, which, on histopathological evaluation, was found to be a mesenteric lymphangioma involving the bowel. Case 2: A 27-year-old male presented with abdominal pain and difficult evacuation. Radiological evaluation revealed a multilobulated lesion involving the mesentery and with differential diagnoses of mesenteric fibromatoses and inflammatory pseudotumor. Histopathological assessment of the resected mass revealed a lymphangioma that was limited to the mesentery. Owing to their rarity and non-specific presentation, mesenteric lymphangiomas are often misdiagnosed on clinical examination and imaging. Thus, histopathological examination is the gold standard to reach a definitive diagnosis.

7.
Biochim Biophys Acta Mol Cell Res ; 1871(4): 119702, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38408543

RESUMO

Inhibition of Reactive Oxygen Species (ROS) is one of the strategies that Mycobacterium tuberculosis (Mtb) employs as its defence mechanism. In this study, the role of PPE15 (Rv1039c), a late-stage protein, has been investigated in modulating the cellular ROS. We discovered PPE15 to be a secretory protein that downregulates ROS generation in THP1 macrophages. Our in-silico analysis revealed the presence of a eukaryote-like SH3 (SH3e) domain in PPE15. The predicted SH3e-domain of PPE15 was found to interact with cytosolic components of NADPH Oxidase (NOX), p67phox and p47phox through molecular docking. In-vitro experiments using THP1 macrophages showed a diminished NADP/NADPH ratio, indicating reduced NOX activity. We also observed increased levels of p67phox and p47phox in the cytoplasmic fraction of PPE15 treated macrophages as compared to the plasma membrane fraction. To understand the role of the SH3e-domain in ROS modulation, this domain was deleted from the full-length PPE15 (PPE15-/-SH3). We observed an increase in cellular ROS and NADP/NADPH ratio in response to PPE15-/-SH3 protein. The interaction of PPE15-/-SH3 with p67phox or p47phox was also reduced in the cytoplasm, indicating migration of NOX subunits to the plasma membrane. Additionally, M. smegmatis expressing PPE15 was observed to be resistant to oxidative stress with significant intracellular survival in THP1 macrophages as compared to M. smegmatis expressing PPE15-/-SH3. These observations suggest that the SH3e-domain of PPE15 interferes with ROS generation by sequestering NOX components that inhibit NOX assembly at the cell membrane. Therefore, PPE15 acts like a molecular mimic of SH3-domain carrying eukaryotic proteins that can be employed by Mtb at late stages of infection for its survival. These findings give us new insights about the pathogen evading strategy of Mtb which may help in improving the therapeutics for TB treatment.


Assuntos
Mycobacterium tuberculosis , Espécies Reativas de Oxigênio/metabolismo , NADP/metabolismo , Domínios de Homologia de src , Simulação de Acoplamento Molecular , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Eucariotos
8.
Sci Rep ; 14(1): 2763, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307873

RESUMO

The Beas River is one of the important rivers of the Indus River system located in Himachal Pradesh, India, that harbors a diverse range of freshwater fish species. The present study employed COI gene to investigate the ichthyofaunal diversity of river Beas. Through the sequencing of 203 specimens from Beas River, we identified 43 species, belonging to 31 genera, 16 families, and 10 orders. To analyze the genetic divergence and phylogeny of identified species, 485 sequences of Indian origin were retrieved from BOLD, resulting in a dataset of 688 sequences. Our findings consistently revealed a hierarchical increase in the mean K2P genetic divergence within species (0.80%), genus (9.06%), and families (15.35%). Automated Barcode Gap discovery, Neighbour Joining, and Bayesian inference consensus tree methodologies were employed to determine the putative species and their phylogeny, successfully delimiting most of the species with only a few exceptions. The results unveiled six species exhibiting high intra-species divergence (> 2%), suggesting the presence of sibling species and falsely identified sequences on online databases. The present study established the first DNA barcoding-based inventory of freshwater fish species in the Beas River providing comprehensive insights into economically exploited endangered and vulnerable species. In order to ensure the sustainable use of aquatic resources in the Beas River, we recommend the implementation of species measures to protect biodiversity and genetic resources.


Assuntos
Código de Barras de DNA Taxonômico , Rios , Humanos , Animais , Código de Barras de DNA Taxonômico/métodos , Teorema de Bayes , Complexo IV da Cadeia de Transporte de Elétrons/genética , Peixes/genética , Água Doce , DNA , Filogenia , Biodiversidade
9.
Brain Res ; 1829: 148797, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38342422

RESUMO

Alzheimer's Disease (AD) represents a complex interplay of neurological pathways and molecular mechanisms, with significant impacts on patients' lives. This review synthesizes the latest developments in AD research, focusing on both the scientific advancements and their clinical implications. We examine the role of microglia in AD, highlighting their contribution to the disease's inflammatory aspects. The cholinergic hypothesis, a cornerstone of AD research, is re-evaluated, including the role of Alpha-7 Nicotinic Acetylcholine Receptors in disease progression. This review places particular emphasis on the neurotransmission systems, exploring the therapeutic potential of GABAergic neurotransmitters and the role of NMDA inhibitors in the context of glutamatergic neurotransmission. By analyzing the interactions and implications of neurotransmitter pathways in AD, we aim to shed light on emerging therapeutic strategies. In addition to molecular insights, the review addresses the clinical and personal aspects of AD, underscoring the need for patient-centered approaches in treatment and care. The final section looks at the future directions of AD research and treatment, discussing the integration of scientific innovation with patient care. This review aims to provide a comprehensive update on AD, merging scientific insights with practical considerations, suitable for both specialists and those new to the field.


Assuntos
Doença de Alzheimer , Receptores Nicotínicos , Humanos , Doença de Alzheimer/metabolismo , Colinérgicos , Neurotransmissores , Transmissão Sináptica , Receptores Nicotínicos/metabolismo
10.
PeerJ ; 12: e16799, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38288463

RESUMO

Background: In 2020, 203 million people experienced neck pain, with a higher prevalence in women. By 2050, it is predicted that neck pain will affect 269 million people, representing a 32.5% increase. Physical rehabilitation is often employed for the treatment of chronic non-specific neck pain (CNSNP) and the associated functional loss. Taping is frequently used as an adjunct treatment alongside primary physical rehabilitation. Unlike kinesio tape (KT), the therapeutic benefits of dynamic tape (DT) have not been thoroughly explored and documented in non-athletic conditions. Therefore, the aim of this trial was to determine the effects of DT on pain, disability, and overall well-being in individuals experiencing CNSNP. Methods: A prospective parallel-group active controlled trial was conducted at a single center, involving 136 patients with CNSNP, randomly allocated in a 1:1 ratio. The sham taping group (STC) received standard physiotherapy care (n = 67) alongside DT without tension, while the dynamic taping group (DTC) (n = 69) underwent standard cervical offloading technique with appropriate tension in addition to standard physiotherapy care. Demographic information and three patient-reported outcome measures (PROMs), namely the Neck Disability Index (NDI), Visual Analogue Scale (VAS), and the World Health Organization-Five Well-Being Index (WHO-5), were collected for each participant at three time points (baseline, four weeks post-taping, and four weeks follow-up). Results: At baseline, no significant differences were observed between the STC and DTC for any outcome measure. Notably, all three PROMs exhibited a significant improvement from baseline to four weeks post-intervention, with moderate to small effect sizes (NDI ηp2 = 0.21, VAS ηp2 = 0.23, and WHO-55 ηp2 = 0.05). The WHO-5 scores for both groups demonstrated improvement from baseline through follow-up (p < 0.001). The NDI and VAS scores ameliorated from baseline to the four weeks post-taping period, with marginal improvements observed during the four weeks follow-up. Conclusion: The incorporation of DT as an adjunct to standard physiotherapy care yielded enhancements in pain levels, functional disability, and well-being among patients with CNSNP when compared to the sham group. However, the sustainability of these improvements beyond the taping period lacks statistical significance and warrants further validation.


Assuntos
Dor Crônica , Cervicalgia , Humanos , Feminino , Cervicalgia/terapia , Qualidade de Vida , Estudos Prospectivos , Dor Crônica/terapia , Pescoço
11.
Mol Cancer Ther ; 23(1): 24-34, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37723046

RESUMO

Therapeutic resistance remains a major obstacle to successful clinical management of diffuse intrinsic pontine glioma (DIPG), a high-grade pediatric tumor of the brain stem. In nearly all patients, available therapies fail to prevent progression. Innovative combinatorial therapies that penetrate the blood-brain barrier and lead to long-term control of tumor growth are desperately needed. We identified mechanisms of resistance to radiotherapy, the standard of care for DIPG. On the basis of these findings, we rationally designed a brain-penetrant small molecule, MTX-241F, that is a highly selective inhibitor of EGFR and PI3 kinase family members, including the DNA repair protein DNA-PK. Preliminary studies demonstrated that micromolar levels of this inhibitor can be achieved in murine brain tissue and that MTX-241F exhibits promising single-agent efficacy and radiosensitizing activity in patient-derived DIPG neurospheres. Its physiochemical properties include high exposure in the brain, indicating excellent brain penetrance. Because radiotherapy results in double-strand breaks that are repaired by homologous recombination (HR) and non-homologous DNA end joining (NHEJ), we have tested the combination of MTX-241F with an inhibitor of Ataxia Telangiectasia Mutated to achieve blockade of HR and NHEJ, respectively, with or without radiotherapy. When HR blockers were combined with MTX-241F and radiotherapy, synthetic lethality was observed, providing impetus to explore this combination in clinically relevant models of DIPG. Our data provide proof-of-concept evidence to support advanced development of MTX-241F for the treatment of DIPG. Future studies will be designed to inform rapid clinical translation to ultimately impact patients diagnosed with this devastating disease.


Assuntos
Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Humanos , Criança , Camundongos , Animais , Glioma Pontino Intrínseco Difuso/tratamento farmacológico , Glioma Pontino Intrínseco Difuso/genética , Glioma Pontino Intrínseco Difuso/metabolismo , Recidiva Local de Neoplasia , Reparo do DNA , Transdução de Sinais , DNA/uso terapêutico , Neoplasias do Tronco Encefálico/tratamento farmacológico , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/patologia
12.
Autops. Case Rep ; 14: e2024470, 2024. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1533854

RESUMO

ABSTRACT Lymphangiomas are rare benign tumors that mainly involve the head and neck region in pediatric patients. Lymphangiomas of the small bowel mesentery in adults are rarer. We present two cases of mesenteric lymphangioma with acute abdominal pain on presentation. Case 1: A 38-year-old female presented with abdominal pain, vomiting, fever, and difficult evacuation. On abdominal examination, she had an ill-defined, tender lump, and radiological findings raised a possibility of perforation peritonitis. Thus, exploratory laparotomy was planned. Per-operatively, a mesenteric mass was found, which, on histopathological evaluation, was found to be a mesenteric lymphangioma involving the bowel. Case 2: A 27-year-old male presented with abdominal pain and difficult evacuation. Radiological evaluation revealed a multilobulated lesion involving the mesentery and with differential diagnoses of mesenteric fibromatoses and inflammatory pseudotumor. Histopathological assessment of the resected mass revealed a lymphangioma that was limited to the mesentery. Owing to their rarity and non-specific presentation, mesenteric lymphangiomas are often misdiagnosed on clinical examination and imaging. Thus, histopathological examination is the gold standard to reach a definitive diagnosis.

13.
J Mech Behav Biomed Mater ; 147: 106145, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37797557

RESUMO

The review paper starts with the introduction to hydrogels along with broad literature survey covering different modes of synthesis including high energy radiation methods. After that, paper covered broad classification of the hydrogels depending upon the basis of their source of origin, method of synthesis, type of cross-linking present and ionic charges on bound groups. Another advanced category response triggered hydrogels, which includes pH, temperature, electro, and light and substrate responsive hydrogels was also studied. Presented paper summarises chemical structure, properties, and synthesis of different kinds of hydrogels. Main focus was given to the preparation super absorbents such as: Semi-interpenetrating networks (semi-IPNs), Interpenetrating networks (IPNs) and cross-linked binary graft copolymers (BGCPs). The weak mechanical properties and easy degradation limit the uses of bio-based -hydrogels in biomedical field. Their properties can be improved through different chemical and physical methods. These methods were also discussed in the current research paper. Also, it includes development of hydrogels as controlled drug delivery devices, as implants and biomaterials to replace malfunctioned body parts along with their use in several other applications listed in the literature. Literature survey on the application of hydrogels in different fields like biomedical, nano-biotechnology, tissue engineering, drug delivery and agriculture was also carried out.


Assuntos
Materiais Biocompatíveis , Hidrogéis , Hidrogéis/química , Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos , Temperatura , Polímeros/química
14.
J Biomol Struct Dyn ; : 1-11, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37811549

RESUMO

2,4-Dibromophenol (DBP) has several industrial applications, including as a wood preservative and flame retardant. This study investigated the interaction between DBP and human hemoglobin (Hb) using spectroscopic, molecular docking and molecular dynamic techniques. The UV-visible spectra showed ground-state complex formation between DBP and Hb. Fluorescence studies revealed that DBP binding caused significant quenching of Hb fluorescence by the static quenching mechanism. The binding of DBP to Hb is a spontaneous process that involves van der Waals forces and hydrogen bonds. There is one DBP binding site on each Hb molecule that is located at the α1ß2 interface of Hb. DBP binding did not alter the microenvironment of tyrosine and tryptophan residues in Hb. Circular dichroism studies revealed that DBP increased the α-helical content of Hb. The intrinsic esterase activity of Hb was inhibited by DBP in a concentration-dependent manner. Molecular docking showed that DBP binds to Hb via hydrogen bonds, hydrophobic, van der Waals and π-π interactions. Molecular dynamics simulation confirmed that the Hb-DBP complex is stable. Overall, the results of this study clearly show that DBP induces structural changes and interferes with the function of Hb. This can have important implications for human health.Communicated by Ramaswamy H. Sarma.

15.
Immunol Cell Biol ; 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37565603

RESUMO

The PE_PGRS proteins have coevolved with the antigenic ESX-V secretory system and are abundant in pathogenic Mycobacterium. Only a few PE_PGRS proteins have been characterized, and research suggests their role in organelle targeting, cell death pathways, calcium (Ca2+ ) homeostasis and disease pathogenesis. The PE_PGRS45 (Rv2615c) protein was predicted to contain mitochondria targeting sequences by in silico evaluation. Therefore, we investigated the targeting of the Rv2615c protein to host mitochondria and its effect on mitochondrial functions. In vitro experiments showed the Rv2615c protein colocalized with the mitochondria and led to morphological mitochondrial perturbations. Recombinant Rv2615c was observed to cause increased levels of intracellular reactive oxygen species and the adenosine diphosphate-to-adenosine triphosphate ratio. The Rv2615c protein also induced mitochondrial membrane depolarization and the generation of mitochondrial superoxide. We observed the release of cytochrome C into the cytoplasm and increased expression of proapoptotic genes Bax and Bim with no significant change in anti-apoptotic Bcl2 in Rv2615c-stimulated THP1 macrophages. Ca2+ is a key signaling molecule in tuberculosis pathogenesis, modulating host cell responses. As reported for other PE_PGRS proteins, Rv2615c also has Ca2+ -binding motifs and thus can modulate calcium homeostasis in the host. We also observed a high level of Ca2+ influx in THP1 macrophages stimulated with Rv2615c. Based on these findings, we suggest that Rv2615c may be an effector protein that could contribute to disease pathogenesis by targeting host mitochondria.

16.
Neoplasia ; 44: 100931, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37647805

RESUMO

Therapeutic resistance remains a major obstacle to preventing progression of H3K27M-altered Diffuse Midline Glioma (DMG). Resistance is driven in part by ALDH-positive cancer stem cells (CSC), with high ALDH1A3 expression observed in H3K27M-mutant DMG biopsies. We hypothesized that ALDH-mediated stemness and resistance may in part be driven by the oncohistone itself. Upon deletion of H3K27M, ALDH1A3 expression decreased dramatically and was accompanied by a gain in astrocytic marker expression and a loss of neurosphere forming potential, indicative of differentiation. Here we show that the oncohistone regulates histone acetylation through ALDH1A3 in a Wnt-dependent manner and that loss of H3K27M expression results in sensitization of DMGs to radiotherapy. The observed elevated Wnt signaling in H3K27M-altered DMG likely stems from a dramatic suppression of mRNA and protein expression of the Wnt inhibitor EYA4 driven by the oncohistone. Thus, our findings identify EYA4 as a bona fide tumor suppressor in DMG that upon suppression, results in aberrant Wnt signaling to orchestrate stemness and differentiation. Future studies will explore whether overexpression of EYA4 in DMG can impede growth and invasion. In summary, we have gained mechanistic insight into H3K27M-mediated regulation of cancer stemness and differentiation, which provides rationale for exploring new therapeutic targets for DMG.

17.
Bioengineered ; 14(1): 2184518, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37498651

RESUMO

In the present era of global climate change, the scarcity of potable water is increasing both due to natural and anthropogenic causes. Water is the elixir of life, and its usage has risen significantly due to escalating economic activities, widespread urbanization, and industrialization. The increasing water scarcity and rising contamination have compelled, scientists and researchers, to adopt feasible and sustainable wastewater treatment methods in meeting the growing demand for freshwater. Presently, various waste treatment technologies are adopted across the globe, such as physical, chemical, and biological treatment processes. There is a need to replace these technologies with sustainable and green technology that encourages the use of microorganisms since they have proven to be more effective in water treatment processes. The present review article is focused on demonstrating how effectively various microbes can be used in wastewater treatment to achieve environmental sustainability and economic feasibility. The microbial consortium used for water treatment offers many advantages over pure culture. There is an urgent need to develop hybrid treatment technology for the effective remediation of various organic and inorganic pollutants from wastewater.


Microbial engineering approaches for wastewater treatment.Current and emerging sources of water pollution are discussed.Various treatment technologies for wastewater treatment.Biological methods and microbes are used for degradation.Parameters responsible for the degradations processes of wastewater.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Purificação da Água , Águas Residuárias , Eliminação de Resíduos Líquidos , Conservação dos Recursos Naturais
18.
J Trace Elem Med Biol ; 80: 127272, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37516010

RESUMO

BACKGROUND: Nickel is a heavy metal that is regarded as a possible hazard to living organisms due to its toxicity and carcinogenicity. Nickel chloride (NiCl2), an inorganic divalent Ni compound, has been shown to cause oxidative stress in cells by altering the redox equilibrium. We have investigated the effect of NiCl2 on isolated human erythrocytes under in vitro condition. METHODS: Isolated erythrocytes were treated with different concentrations of NiCl2 (25-500 µM) for 24 h at 37 ºC. Hemolysates were prepared and several biochemical parameters were analyzed in them. RESULTS: Treatment of erythrocytes with NiCl2 enhanced the intracellular generation of reactive oxygen species (ROS). A significant increase in hydrogen peroxide levels and oxidation of proteins and lipids was also seen. This was accompanied by a reduction in levels of nitric oxide, glutathione, free amino groups and total sulfhydryl groups. NiCl2 treatment impaired both enzymatic and non-enzymatic defense systems, resulting in lowered antioxidant capacity and diminished ability of cells to quench free radicals and reduce metal ions. NiCl2 exposure also had an inhibitory effect on the activity of enzymes involved in pathways of glucose metabolism (glycolytic and pentose phosphate shunt pathways). Increased level of methemoglobin, which is inactive in oxygen transport, was also seen. The rate of heme breakdown increased resulting in the release of free iron. Exposure to NiCl2 led to considerable cell lysis, indicating damage to the erythrocyte membrane. This was supported by the inhibition of membrane bound enzymes and increase in the osmotic fragility of NiCl2 treated cells. NiCl2 treatment caused severe morphological alterations with the conversion of normal discocytes to echinocytes. All changes were seen in a NiCl2 concentration-dependent manner. CONCLUSION: NiCl2 generates cytotoxic ROS in human erythrocytes which cause oxidative damage that can decrease the oxygen carrying capacity of blood and also lead to anemia.


Assuntos
Níquel , Estresse Oxidativo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Níquel/toxicidade , Níquel/metabolismo , Eritrócitos/metabolismo , Oxigênio/metabolismo , Oxigênio/farmacologia
19.
Neurodiagn J ; 63(3): 205-214, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37506256

RESUMO

Background: The intensive physical regimen followed by throwers and archers can impose stress on the elbow and hand in particular positions, which may increase the risk of developing peripheral nerve disorders and symptoms like pain and numbness. Purpose: The purpose of the study is to investigate the effect of forearm and elbow joint positions on ulnar nerve conduction velocity in throwers, archers, and non-athletes. Method: Total 34 subjects both males and females were included with body mass index (BMI) between 18.5 and 24.9 kg/m2. Nerve conduction study (NeuroStim NS2 EMG/NCV/EP System) was used for measuring ulnar nerve conduction velocity (NCV) across elbow joint at different angles (0° elbow extension, 45°, 90°, and 120° elbow flexion) with different forearm positions. Result: Repeated Measure Analysis of Variance (RMANOVA) revealed that there was a statistically significant difference in mean values of ulnar NCV at different angles, forearm positions & groups (p < .05). Conclusion: The forearm and elbow positions can have a significant impact on ulnar NCV, especially in athletes who perform repetitive upper limb motions. Results showed that the archers had significantly slower NCV than throwers and non-athletes at 90° of elbow flexion and forearm pronation.


Assuntos
Articulação do Cotovelo , Antebraço , Masculino , Feminino , Humanos , Antebraço/fisiologia , Nervo Ulnar , Condução Nervosa/fisiologia , Extremidade Superior
20.
Artigo em Inglês | MEDLINE | ID: mdl-37247154

RESUMO

In the present study, phytoextraction of a weed plant, Parthenium hysterophorus, was performed through aqueous, alcoholic and hydroethanolic (80%) solvents followed by phytochemical profiling and evaluation of median lethal concentration (LC50) of hydroethanolic extract in a freshwater fish, common carp (Cyprinus carpio). Haemato-physiological response was also evaluated based on LC50 (18.99 mg L-1) at two sub-lethal concentrations of extract [T1: 0.379 mg L-1 (LC50/50), T2: 0.759 mg L-1 (LC50/25) and a control: devoid of extract] at three intervals (24, 48 and 96 h). The study revealed toxic constituents in extracts and the superior extraction ability of hydroethanolic solvent which was chosen for further biological characterisation, particularly on haematotoxicity. The anti-bacterial assay revealed the inhibitory capacity of the extract, whereas the phyto-haemagglutination assay, haemagglutination limit test and haemolytic activity revealed clumping, agglutination (at 1/96th dilution) and lytic capability of extract, respectively. Later, in vivo analyses revealed a significant modulation in haemato-immunological and serum biochemical parameters upon hydroethanolic extract exposure. In conclusion, the present study emphasises locally available gajar ghas, P. hysterophorus as a non-chemical phyto-ichthyotoxin towards sustainable aquaculture.

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