Outbreaks of emerging infectious diseases continue to challenge human health. Novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has triggered a global coronavirus pandemic, known as ...COVID-19. Multiple variants of SARS-CoV-2 virus are circulating, thus raising questions with respect to the effectiveness of different lines of treatment, such as vaccines and antiviral drugs. To find the appropriate prevention/treatment, 21 plant-based ingredients (Glycyrrhizin, Withanone, Aloe-emodin, Rhein, Emodin, Chrysophanol, Physcion, Kaempferol, Progallin A, Gallic acid, Naringin, Quercetin, Luteolin, and Apigenin) having antiviral, antibacterial and antifungal properties were identified. We pseudo-typed SARS-CoV-2 on a lentiviral vector plasmid and tested the impact of five different herbal formulations in mammalian HEK293T cells. Viral inactivation assay showed that the natural extracts in a herb-derived phytoconstituent-based formulation, BITS-003, comprising Bacopa monnieri, Glycyerrhiza glabra, Asparagus racemosus-wild, and Nigella sativa had strong virucidal properties, inactivating enveloped viruses from 2log10 (or 99%) to >4log10 (or 99.99%). Moreover, bacterial and yeast cells treated with BITS-003 displayed reduced growth. Topical use of the formulation as a mouthwash/gargle could be effective in reducing symptoms of respiratory viral infections, with the potential to decrease the viral load in the buccal/oral cavity. This may inhibit the coronavirus spreading to the lungs of infected persons and at the same time may reduce the risk of viral transmission to other susceptible persons through micro-droplets originating from the oral cavity of the infected person.
The androgen receptor is one of the key targets for prostate cancer treatment. Despite its less satisfactory effects, chemotherapy is the most common treatment option for metastatic and/or ...castration-resistant patients. There are constant needs for novel anti-prostate cancer therapeutic/prevention agents. Curcumin, a known chemo-preventive agent, was shown to inhibit prostate cancer cell growth. This study aimed to unravel the inhibitory effect of curcumin in prostate cancer through analyzing the alterations of expressions of curcumin targeting genes clusters in androgen-dependent LNCaP cells and androgen-independent metastatic C4-2B cells. Hierarchical clustering showed the highest number of differentially expressed genes at 12 h post treatment in both cells, suggesting that the androgen-dependent/independent manner of curcumin impacts on prostate cancer cells. Evaluation of significantly regulated top canonical pathways highlighted that Transforming growth factor beta (TGF-β), Wingless-related integration site (Wnt), Phosphoinositide 3-kinase/Protein Kinase B/ mammalian target of rapamycin (PIK3/AKT(PKB)/mTOR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling were primarily inhibited, and Phosphatase and tensin homolog (PTEN) dependent cell cycle arrest and apoptosis pathways were elevated with curcumin treatment. The short term (3-24 h) and long term (48 h) effect of curcumin treatment revealed 31 and four genes modulated in both cell lines. TGF-β signaling, including the androgen/TGF-β inhibitor Prostate transmembrane protein androgen-induced 1 (
), was the only pathway impacted by curcumin treatment after 48 h. Our findings also established that
Proto-Oncogene, basic helix-loop-helix (bHLH) Transcription Factor (MYC) signaling was down-regulated in curcumin-treated cell lines. This study established, for the first time, novel gene-networks and signaling pathways confirming the chemo-preventive and cancer-growth inhibitory nature of curcumin as a natural anti-prostate cancer compound.
Obesity and hyper-intestinal permeability are interconnected. This study is designed to evaluate the ability of Mangifera indica seed kernel extract (MESK) in restoring the intestinal barrier and ...preventing obesity and associated metabolic complications in a high-fat diet-induced obese mouse model. Four groups of Swiss albino mice: (1) normal diet (ND), (2) high-fat diet (HFD), (3) HFD + Orlistat (100 µg/kg), and (4) HFD + MESK (75 µg/kg), were used to monitor various biochemical parameters associated with metabolic syndrome (glucose, total cholesterol, triglycerides) and body weight in an eight-week-long study. In vivo intestinal permeability was determined by the FITC-dextran method. Interestingly, MESK significantly reduced HFD-induced body weight gain, hepatic lipid accumulation, hepatic fibrosis, hyperglycemia, and dyslipidemia. Additionally, MESK treatment restored the expression of tight junction protein Zonula Occludens-1 (ZO-1) and Claudin-1 and hence prevented increased intestinal permeability induced by a high-fat diet. Moreover, it also increased the expression of potent satiety molecule Nesfatin-1 in the mouse jejunum. Our results, for the first time, establish MESK as a nutraceutical which prevents disruption of the intestinal barrier and thereby intercepts the adverse consequences of compromised intestinal permeability such as obesity, hyperglycemia, dyslipidemia, and systemic inflammation.
Antisense Therapy offers a comprehensive, state-of-the art perspective on the role of antisense therapy in the treatment of human disease, with a special focus on cancer. Use of antisense ...oligonucleotides is a growing field of pharmaceutical and biotech companies and research programs for treatment of several diseases. This book summarizes and presents the best updates, therapeutic principles, methods, and applications in the field and offers meaningful information to move treatment discovery forward.
The identification of prostate transmembrane protein androgen induced 1 (
), an androgen responsive gene, came initially from the studies of androgen regulatory gene networks in prostate cancer. It ...was soon followed by the documentation of the expression and functional analysis of transmembrane prostate androgen-induced protein (
)/
in other solid tumors including renal, colon, breast, lung, and ovarian cancers. Further elucidation of
gene expression and sequence analysis revealed the presence of five isoforms with distinct extracellular domains (isoforms
,
,
,
, and
). Notably, the predicted amino acid sequences of PMEPA1 isoforms show differences at the N-termini, a conserved membrane spanning and cytoplasmic domains.
serves as an essential regulator of multiple signaling pathways including androgen and TGF-β signaling in solid tumors. Structure-function studies indicate that specific motifs present in the cytoplasmic domain (PY, SIM, SH3, and WW binding domains) are utilized to mediate isoform-specific functions through interactions with other proteins. The understanding of the "division of labor" paradigm exhibited by
isoforms further expands our knowledge of gene's multiple functions in tumorigenesis. In this review, we aim to summarize the most recent advances in understanding of
isoform-specific functions and their associations with prostate cancer progression, highlighting the potentials as biomarker and therapeutic target in prostate cancer.
The immunological findings from autopsies, biopsies, and various studies in COVID-19 patients show that the major cause of morbidity and mortality in COVID-19 is excess immune response resulting in ...hyper-inflammation. With the objective to review various mechanisms of excess immune response in adult COVID-19 patients, Pubmed was searched for free full articles not related to therapeutics or co-morbid sub-groups, published in English until 27.10.2020, irrespective of type of article, country, or region. Joanna Briggs Institute's design-specific checklists were used to assess the risk of bias. Out of 122 records screened for eligibility, 42 articles were included in the final review. The review found that eventually, most mechanisms result in cytokine excess and up-regulation of Nuclear Factor-κB (NF-κB) signaling as a common pathway of excess immune response. Molecules blocking NF-κB or targeting downstream effectors like Tumour Necrosis Factor α (TNFα) are either undergoing clinical trials or lack specificity and cause unwanted side effects. Neutralization of upstream histamine by histamine-conjugated normal human immunoglobulin has been demonstrated to inhibit the nuclear translocation of NF-κB, thereby preventing the release of pro-inflammatory cytokines Interleukin (IL) 1β, TNF-α, and IL-6 and IL-10 in a safer manner. The authors recommend repositioning it in COVID-19.
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e16580
Background: Dysfuncitons of androgen and TGF-β signaling play important roles in prostate tumorigenesis. PMEPA1 gene has been defined as an androgen and TGF-β responsive gene ...which inhibits androgen and TGF-β signaling via negative feed-back loops. Our previous data has established that PMEPA1 distinct isoforms ( PMEPA1-a and PMEPA1-b) with disparities within N-terminus protein sequences navigate different androgen/TGF-β signaling regulations. In this study, the roles of PMEPA1 isoforms in disease progressions were investigated in solid tumors of prostate (CaP), breast, lung and colon. Methods: RNA seq data from total 2479 solid tumor samples in the TCGA dataset were used to study the correlation between expressions of PMEPA1 isoforms and disease progression including Gleason score, pathology stages, progression free survival rate (PFS) and overall survival rate (OS). The cohort is composed of 482 prostate, 1049 breast, 499 lung and 449 colon cancer patients. Results: In CaP, the TCGA data analysis showed that lower transcript level of PMEPA1-b isoform associated with higher Gleason scores and lower progression free survival rate (PFS) (P = 0.014) and worse overall survival rate (OS) (P < 0.01). The ratio of mRNA levels of PMEPA1-a versus PMEPA-b indicated higher Gleason score, lower PFS rate (P = 0.0063) and worse OS rate (P = 0.0042). In contrast, higher expression of both PMEPA1-a and PMEPA- b associated with lower PFS (P = 0.023 and 0.028, respectively) in breast cancer. And the enhanced ratio of PMEPA1-a/ b was also found to indicate lower PFS (P = 0.016) and worse OS (P = 0.016) in breast cancer. Similarly, the increased transcript levels of PMEPA1-a and PMEPA1-b isoforms significantly associated with lower PFS and worse OS rates in lung and colon cancer. The expression of PMEPA1 isoforms was not found to associate with pathology stages of diseases. Conclusions: Our data establish the biomarker potential of PMEPA1 gene isoforms ( a and b) indicating more aggressive disease progressions in 4 solid tumors, further underscoring the PMEPA1 isoform specific biological functions to differentiate regulation of androgen and TGF-β signaling in cancer cells.
Ionizing radiation (IR) from terrestrial sources is continually an unprotected peril to human beings. However, the medical radiation and global radiation background are main contributors to human ...exposure and causes of radiation sickness. At high-dose exposures acute radiation sickness occurs, whereas chronic effects may persist for a number of years. Radiation can increase many circulatory, age related and neurodegenerative diseases. Neurodegenerative diseases occur a long time after exposure to radiation, as demonstrated in atomic bomb survivors, and are still controversial. This review discuss the role of IR in neurodegenerative diseases and proposes an association between neurodegenerative diseases and exposure to IR.
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