HIV and Alcohol Synergistically Disrupt Lysosomal Function in Hepatocytes, Driving Extracellular Vesicle Release and Liver Injury | Chapter 11 | Disease and Health: Research Developments Vol. 10

Although the etiologies of hepatic complications among people living with HIV who consume alcohol are multifactorial, alcohol remains a relatively understudied contributor to the progression of HIV-related liver injury. Here, we investigated whether metabolically derived acetaldehyde impairs lysosomes and releases exosomes to enhance HIV-induced hepatotoxicity. Cytochrome P450 2E1 (CYP2E1)-expressing Huh 7.5 (also known as RLW) cells were exposed to an acetaldehyde-generating system (AGS) for 24 h. We then infected (or not) the cells with HIV-1ADA, then exposed them again to AGS for another 48 h. Lysosome damage was assessed by galectin 3/LAMP1 co-localisation and cathepsin leakage. Additionally, we measured the co-localisation of DRAM 1 and Bax in lysosomes, indicating the contribution of HIV-AGS-triggered lysosomal damage to apoptosis induction in hepatocytes. Expression of lysosome biogenesis–transcription factor, TFEB, was measured by its protein levels and in situ immunofluorescence. Exposure of cells to AGS + HIV caused the greatest amount of lysosome leakage and impaired lysosomal biogenesis, leading to intrinsic apoptosis. Furthermore, AGS exposure impaired the microtubule-dependent translocation of TFEB from the cytosol to the nucleus. This appeared to result from the acetylation of α-tubulin.

Moreover, ZKSCAN3, a repressor of lysosome gene activation by TFEB, was amplified by AGS. Both these changes contributed to AGS-elicited disruption of lysosome biogenesis and promoted exosome release from hepatocytes. These results demonstrate that acetaldehyde impairs lysosomal integrity and repair, promotes exosome release, and exacerbates HIV-induced hepatotoxicity, offering mechanistic insight into alcohol’s role as a co-factor in liver damage among people with HIV.

 

Author (s) Details

Moses New-Aaron
Department of Environmental Health, Occupational Health and Toxicology, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, USA and Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, 615 Michael St. (Suite 205), Atlanta, GA 30322, United States of America.

 

Paul G. Thomes

Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA and Auburn University, Auburn, Alabama, United States of America.

 

Raghubendra Singh Dagur
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.

 

Kharbanda K. Kusum
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA and Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.

 

Larisa Y. Poluektova
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68105, USA.

 

Natalia A. Osna
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA and Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68105, USA.

 

 

Please see the book here:- https://doi.org/10.9734/bpi/dhrd/v10/5390

Connexin26 is Present in Rat Cardiomyocytes and Rat Cardiomyocyte Extracellular Vesicles| Chapter 5 | Current Overview on Disease and Health Vol. 7

 In this episode, we describe the results obtained from our two, currently published studies that aimed to demonstrate the appearance of Cx26 and its immunolocalization in informer cardiomyocytes, in differentiated (d)H9c2 cardiac rat containers and in extracellular vesicles from dH9c2 cell light in weight. Connexins (Cxs) are a family of membrane-traversing proteins, expressed easily intimidated and named according to their microscopic weight. They are famous to form gap junctions, sheath channels mediating container-cell communication, which play an essential part in the propagation of energetic activity in the heart. Cx26 has existed described in any of tissues and its mutations are frequently guide deafness and skin diseases. Only currently, Cx26 has been described in the essence, at level of vessels and cardiomyocytes, and allure localization is scattered all over the container at the level of different subcellular compartments apart from at the intercalated discs as is the case for the other cardiac Cxs. The working characterization of Cx26 in cardiomyocytes debris poorly understood due to this current discovery in the courage tissues. However, the peculiar localization at the level of extracellular vesicles suggested a particular role for cardiac Cx26 in bury-cellular communication in a break junction liberated manner.

Author(s) Details:

Alessandra Falleni,
Department of Clinical and Experimental Medicine, University of Pisa, Italy.

Antonella Cecchettini,
Department of Clinical and Experimental Medicine, University of Pisa, Italy.

Margherita Bernardeschi,
Italian Institute of Technology, Center for Materials Interfaces, Smart Bio-Interfaces, Pontedera, Italy.

Stefania Moscato,
Department of Clinical and Experimental Medicine, University of Pisa, Italy.

Letizia Mattii,
Department of Clinical and Experimental Medicine, University of Pisa, Italy.

Please see the link here: https://stm.bookpi.org/CODH-V7/article/view/9079

Epigenetic Sensitisation of Chemotherapeutic Compounds in Non- Small Cell Lung Cancer | Book Publisher International

 Lung cancer is now the leading cause of cancer-related death worldwide, with 1.7 million fatalities in 2018. The most common kind of lung cancer is non-small cell carcinoma (NSCLC), which accounts for about 80% of all occurrences. In most countries, chemotherapy is still the first-line treatment for NSCLC patients. Chemotherapy is expected to be utilised for at least another two decades, despite the development of novel medicines (targeted chemicals, immunotherapy). Chemotherapy resistance is one of the key variables contributing to lung cancer mortality, and it has been well established in preclinical investigations and clinical trials to date. Currently, there are only a few biomarkers for predicting chemotherapy efficacy, most of which are clinical. Furthermore, clinically, sensitization of cancer cells to such chemicals is largely useless. This research looks into new ways for lung cancer cells to become sensitive to four standard chemotherapeutics (cisplatin, carboplatin, gemcitabine, and vinorelbine), with a focus on epigenetics and the involvement of extracellular vesicles. Cloning, inducible transgene expression, shRNA-based silencing, proliferation and apoptosis assays, the neutral comet assay, RT-qPCR, pyrosequencing-based DNA methylation analysis, and other molecular and cell biology methods (cloning, inducible transgene expression, shRNA-based silencing, proliferation and apoptosis assays, the neutral comet assay, RT-qPCR I examined a wide range of factors in connection to drug resistance in NSCLC cell lines (e.g., western blots, EV isolation and characterization). Resistant cell lines were chosen for sensitization with epigenetic medicines (VPA and DAC), aminomethylphosphonic acid (AMPA), and fendiline after the IC50 of each of the four medications was determined in eight NSCLC cell lines.

VPA showed strong chemotherapeutic sensitization potential for all four chemotherapeutics, which is a first for lung cancer cells. In cells treated with cisplatin or carboplatin, both VPA and DAC caused a considerable increase in apoptotic activity. Gemcitabine produced double strand DNA breaks in the NSCLC cell lines A549, CALU-6, and COR-L23, and pre-treatment with VPA amplified this impact, which was also a novel discovery in this investigation.

I also looked at the role of LANCL1-AS1, a long-noncoding RNA that was shown to be reduced in NSCLC tissues by our research team. Following the establishment of an inducible expression model in the SK-MES-1 cell line, it was discovered that LANCL1-AS1 induced an increase in proliferation rate, migration invasion, sensitivity to gemcitabine and vinorelbine, increased resistance to platin compounds, and, most notably, expression of its coding counterpart gene, LANCL1. The LANCL1 shRNA-based silencing resulted in a reduction in proliferation, migration, and oxidative stress sensitivity. However, sensitivity to all four medications followed the same pattern as overexpression of LANCL1-AS1, raising doubts about whether these two activities are connected or separate, with no way to rule out the possibility of off-target effects from the shRNA method at this time.

The function of extracellular vesicles (EVs) in cancer development and medication resistance has just lately been studied. As a result, I decided to see if the LANCL1-AS1-dependent gemcitabine sensitivity could be transferred to EVs. Increased LANCL1-AS1 expression resulted in a dose-dependent increase in EV release. Unfortunately, due to a variety of technical concerns with the EV isolation reagent's toxicity, knowledge of how LANCL1-AS1 produced EVs affect gemcitabine resistance when transmitted to a recipient cell line was not possible. Finally, this research has revealed some new insights towards sensitising NSCLC cells in a preclinical setting. More research is needed to determine whether these findings are clinically useful and how they might alter lung cancer treatment.

Author(s) Details

Ghaliah Obaid F. Alnefaie
Medical Genetic Department, Taif University, Taif, Saudi Arabia.

View Book:- https://stm.bookpi.org/ESCCNSCLC/article/view/1837

Impact of Alcohol Exposure on the Composition of HeLa-Derived Extracellular Vesicles | Chapter 14 | Recent Progress in Microbiology and Biotechnology Vol. 5

 Extracellular vesicles are nanosized vesicles whose function in intercellular communication is being studied extensively. Extracellular vesicles are being studied for their potential as disease biomarkers and/or vaccine agents, as well as their function in disease defence. Since cervical cancer has such a high mortality rate, more research about how to diagnose and treat the disease is required. Several researchers have begun to look into extracellular vesicles and their function in disease defence in this regard. The aim of this study was to see how alcohol affected the biogenesis and composition of extracellular vesicles derived from the HeLa cervical cancer cell line. HeLa cells were cultured in exosome-free media and either mock-treated (control) or treated with 50 mM or 100 mM alcohol for 24 and 48 hours, respectively. Alcohol has an important effect on HeLa cell viability and exosome biogenesis/composition, according to our findings. Our findings show that alcohol has a significant impact on HeLa cells, as well as the biogenesis and composition of HeLa-derived extracellular vesicles. These findings show that alcohol affects the packaging of heat shock proteins and apoptotic proteins in extracellular vesicles. Extracellular vesicles are both communicators for HeLa cells and biomarkers for the disease's onset and progression. The research results may have significant effects on diagnostics and therapy for a variety of cell types and organ systems, as HeLa cells were used as the primary model in this study. To elucidate the mechanism(s) involved in these processes, further research is needed.

Author (s) Details

Leandra B. Jones
Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.

Sanjay Kumar
Department of Pediatrics and Cell, Developmental and Integrative Biology, Division of Neonatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Aliyah J. Curry
Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA and Center for Nanobiotechnology Research (CNBR), Alabama State University, Montgomery, AL 36104, USA.

Jayde S. Price
Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA and Center for Nanobiotechnology Research (CNBR), Alabama State University, Montgomery, AL 36104, USA.

Alexandre Krendelchtchikov
Department of Pediatrics and Cell, Developmental and Integrative Biology, Division of Neonatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Brennetta J. Crenshaw
Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.

Courtnee’ R. Bell
Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.

Sparkle D. Williams
Department of Pediatrics and Cell, Developmental and Integrative Biology, Division of Neonatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Tambre A. Tolliver
Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.

Sabita N. Saldanha
Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.

Brian Sims
Department of Pediatrics and Cell, Developmental and Integrative Biology, Division of Neonatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Qiana L. Matthews
Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA and Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.

View Book :- https://stm.bookpi.org/RPMB-V5/article/view/877