Current Pharmaceutical Biotechnology - Volume 23, Issue 2, 2022

Background: Crotalicidin (Ctn), a snake venom cathelicidin-related antimicrobial peptide, is a 34-residue-long linear lysine-rich vipericidin obtained from the South American rattlesnake, Crotalus durissus terrificus. Ctn contains tandem repeats of nine amino acid residues (1KRFKKFFKK9 and 16KRLKKIFKK24; consensus: 1KRhKKhFKK9, h = hydrophobic amino acid) as an integral part of its structure. Objectives: The aim of this study was to evaluate the antimicrobial activity of the encrypted vipericidin nonapeptide KRFKKFFKK, designated as Ctn[1-9], and its structural analogue, rhodamine- B-conjugated Ctn[1-9], designated as RhoB-Ctn[1-9]. Methods: The susceptibility of representative pathogenic bacteria and yeasts to antimicrobial agents was determined using the broth microdilution minimum inhibitory concentration (MIC) method. Cytotoxicity was estimated using a hemolytic assay. The accumulation of RhoB-Ctn[1-9] in microbial cells was observed by fluorescence microscopy. The antimicrobial synergism of RhoB-Ctn[1-9] with antimicrobials was evaluated using a checkerboard analysis. Results: RhoB-conjugated Ctn[1-9] displayed selective antimicrobial activity against infectious gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, and pathogenic species of Candida with low hemolytic effects on human erythrocytes which were not observed with unconjugated Ctn[1-9]. RhoB-Ctn[1-9] could permeate cell membranes and accumulate intracellularly in microbial cells. RhoB-Ctn[1-9] exhibits synergistic effects when used with antibiotics or antifungal agents and reduced the MICs of the peptide and antimicrobials. Conclusion: These findings indicate the potential of crotalicidin-related short peptides as structural motifs for the diversification of biological functionalities. Further, they set the stage to investigate the molecular mechanisms by which chemically modified vipericidin repeats modulate cell fate.

Physical exercise (PE), notoriously, promotes a state of general well-being, throughout the entire human lifespan. Moreover, maintaining an adequate and regular PE habit results in a powerful preventive factor towards many diseases and may also help in managing existing pathological conditions. PE induces structural and functional changes in various parts of the body, determining biological and psychological benefits. Additionally, in the elderly, PE might represent a remarkable tool reducing cognitive impairments related to the normal aging processes and it has also been found to have an impact on neurodegenerative diseases such as Alzheimer’s disease. The present review aims to provide an overview of PE effects on the hippocampus, since it is one of the brain regions most susceptible to aging and, therefore, involved in diseases characterized by cognitive impairment.

Cardiovascular diseases are some of the major causes of morbidity and mortality in developed and developing countries. Cardiac fibrosis is one of the most often pathological changes of heart tissues. It occurs as a result of extracellular matrix proteins accumulation at myocardia. Cardiac fibrosis results in impaired cardiac systolic and diastolic functions and is associated with other effects. Therapies with medicines have not been sufficiently successful in treating chronic diseases such as CVD. Therefore, the interest for therapeutic potential of natural compounds and medicinal plants has increased. Plants such as grapes, berries and peanuts contain a polyphenolic compound called "resveratrol" which has been reported to have various therapeutic properties for a variety of diseases. Studies on laboratory models show that resveratrol has beneficial effects on cardiovascular diseases, including myocardial infarction, high blood pressure cardiomyopathy, thrombosis, cardiac fibrosis, and atherosclerosis. In vitro animal models using resveratrol indicated protective effects on the heart by neutralizing reactive oxygen species, preventing inflammation, increasing neoangiogenesis, dilating blood vessels, suppressing apoptosis and delaying atherosclerosis. In this review, we are presenting experimental and clinical results of studies concerning resveratrol effects on cardiac fibrosis as a CVD outcome in humans.

Months after WHO declared COVID-19 as a Global Public Health Emergency of International Concern, it does not seem to be flattening the curve as we are still devoid of an effective treatment modality and vaccination is in the first phase in many countries. Amid such uncertainty, being immune is the best strategy to defend against corona attacks. As the whole world is referring back to immune-boosting traditional remedies, interest is rekindled in the Indian system of Medicine, which is gifted with an abundance of herbal medicines as well as remedies. Among them, spices (root, rhizome, seed, fruit, leaf, bud, and flower of various plants used to add taste and flavors to food) are bestowed with immense medicinal potential. A plethora of clinical as well as preclinical studies reported the effectiveness of various spices for various ailments. The potential immune-boosting properties together with their excellent safety profiles are making spices the current choice of phytoresearch as well as the immune-boosting home remedies during these sceptical times. The present review critically evaluates the immune impact of various Indian spices and their potential to tackle the novel coronavirus, with comments on the safety and toxicity aspects of spices.

Endometrial cancer represents the most frequent neoplasia from the corpus uteri and comprises the 14th leading cause of death in women worldwide. Risk factors that contribute to the disease include early menarche, late menopause, nulliparity, and menopausal hormone use, as well as hypertension and obesity comorbidities. The clinical effectiveness of chemotherapy is variable, suggesting that novel molecular targeted therapies against specific cellular processes associated with the maintenance of cancer cell survival and therapy resistance ameliorate the rates of success in endometrial cancer treatment. In the course of tumor growth, cancer cells must adapt to decreased oxygen availability in the microenvironment by upregulation of hypoxia-inducible factors, which orchestrate the activation of a transcriptional program leading to cell survival. During this adaptative process, the hypoxic cancer cells may acquire invasive and metastatic properties as well as increased cell proliferation and resistance to chemotherapy, enhanced angiogenesis, vasculogenic mimicry, and maintenance of cancer cell stemness, which contribute to more aggressive cancer phenotypes. Several studies have shown that hypoxia-inducible factor 1 alpha (HIF-1α) protein is aberrantly overexpressed in many solid tumors of the breast, prostate, ovarian, bladder, colon, brain, and pancreas. Thus, it has been considered an important therapeutic target. Here, we reviewed the current knowledge of the relevant roles of cellular hypoxia mechanisms and HIF-1α functions in diverse processes associated with endometrial cancer progression. In addition, we also summarize the role of microRNAs in the posttranscriptional regulation of protein-encoding genes involved in the hypoxia response in endometrial cancer. Finally, we pointed out the need for urgent targeted therapies to impair the cellular processes activated by hypoxia in the tumor microenvironment.

The world population has suffered as a result of the COVID-19 pandemic. The disease has become life-threatening in a very short time, harming citizens and the economic systems globally. The novel virus SARS-CoV-2 has been known as the causative agent of COVID-19. The SARS-CoV-2 is a single-stranded RNA virus having ~30 kb genomic components, which are 70% identical to SARS-CoV. The main process of the pathophysiology of COVID-19 has been associated with the interaction of a novel coronavirus with host cell receptor, angiotensin-converting enzyme-2 (ACE 2), by fusion. Therapeutic agents having serine protease inhibitors and ACE-2 blockers may be explored for the treatment by inhibiting the viral target such as Mpro, RdRp, PLpro, and helicase. Herbal medicine has a wide array of chemical entities with potential health benefits, including antiviral activity, which may be explored as an alternative treatment for COVID-19. The herbal bioactives like catechins, andrographolide, hesperidin, biorobin, scutellarein, silvestrol, shikonin, tryptanthrin, vitexin quercetin, myricetin, caffeic acid, psoralidin, luteolin, etc. have shown potential inhibitory effect against SARS-CoV-2. Recent research reports indicate that the various plant secondary metabolites have shown potential antiviral activities. The present review article highlights the recent information on the mechanism of actions and applications of herbal medicine in the treatment of COVID-19.

The Mediterranean diet is appraised as the premier dietary regimen, and its espousal is correlated with the prevention of degenerative diseases and extended longevity. The consumption of olive oil stands out as the most peculiar feature of the Mediterranean diet. Olive oil rich in various bioactive compounds like oleanolic acid, oleuropein, oleocanthal, and hydroxytyrosol is known for its antiinflammatory as well as cardioprotective property. Recently in silico studies have indicated that phytochemicals present in olive oil are a potential candidate to act against SARS-CoV-2. Although there are many extensive studies on olive oil and its phytochemical composition, however, some lacunas persist in understanding how the phytochemical composition of olive oil is dependent on upstream processing. The signaling pathways regulated by olive oil in the restriction of various diseases are also not clear. For answering these queries, a detailed search of research and review articles published between 1990 to 2019 were reviewed. Olive oil consumption was found to be advantageous for various chronic non-communicable diseases. Olive oil’s constituents are having potent anti-inflammatory activities and thus restrict the progression of various inflammation-linked diseases ranging from arthritis to cancer. But it is also notable that the amount and nature of the phytochemical composition of household olive oil are regulated by its upstream processing, and the physicochemical properties of this oil can give a hint regarding the manufacturing method as well as its therapeutic effect. Moreover, daily uptake of olive oil should be monitored as excessive intake can cause body weight gain and a change in the basal metabolic index. So, it can be concluded that the olive oil consumption is beneficial for human health, and particularly for the prevention of cardiovascular diseases, breast cancer, and inflammation. The simple way of processing olive oil is to maintain the polyphenol constituents, whichprovide the protection against noncommunicable diseases and SARS-CoV-2.

Background: Dihydroartemisinin (DHA) exhibited anti-tumor effect in a variety of cancer cells, but its mechanism of action is unclear. Objectives: To investigate the therapeutic effects of DHA on Cisplatin (DDP)-resistant gastric cancer cell strain SGC7901/DDP and the possible molecular mechanism. Methods: Cells were treated with DHA in a dose- and time-dependent manner, after which their proliferation, apoptosis, invasion, and migration abilities were evaluated. We further evaluated autophagy with mRFP-GFP-LC3 adenovirus transfection and transmission electron microscopy and also detected the expression levels of proteins (related to autophagy and apoptosis) via western blot. Meanwhile, the influence of DHA on cisplatin resistance was detected through a sensitization test and the evaluation of P-gp expression levels. Results: DHA effectively inhibited the proliferation, invasion, and migration of SGC7901/DDP cells and induced cell apoptosis which was accompanied by caspase-8/9/3 activation. Furthermore, exposure to DHA resulted in a pronounced increase in autophagy proteins, including Beclin-1 and LC3 II with PI3K/AKT/mTOR pathway inhibition. Additionally, enhancement of cisplatin sensitivity occurred in SGC7901/DDP cells treated with DHA, which was accompanied by P-gp downregulation. Conclusion: DHA exerts an anti-cancer effect on SGC7901/DDP cells and the mechanisms possibly include enhancement of autophagy via PI3K/AKT/mTOR inhibition, inducement of apoptosis through caspase-dependent and mitochondrial pathway, and enhancement of cisplatin sensitivity through P-gp inhibition.

Background: Sulfur Mustard is a strong vesicant and chemical warfare agent that imposes toxicity to the lungs, eyes, and skin after accidental or intended exposure. Objectives: The current study was intended to explore in vitro and in vivo decontamination properties of electrolytically generated HOCl (hypochlorous acid) against CEES (2-chloroethyle ethyle sulphide), a known sulfur mustard simulant & vesicating agent. Methods: in vitro studies were carried out using UV spectroscopy and GC-MS methods. In vivo studies were performed in Strain A and immune-compromised mice by subcutaneous as well as prophylactic topical administration of HOCl pretreated CEES. The blister formation and mortality were considered as end-point. Histopathological study was conducted on skin samples by H & E method. DNA damage studies measuring γ-H2AX and ATM have been carried out in human blood using flow cytometry. Anti-bacterial action was tested by employing broth micro dilution methods. A comparative study was also carried out with known oxidizing agents. Results: The topical application of pre-treated CEES at 5, 30 min and 1 h time points showed significant (p<0.001) inhibition of blister formation. DNA damage study showed reduced mean fluorescence intensity of DSBs nearly 17-20 times, suggesting that HOCl plays a protective role against DNA damage. Histopathology showed no sign of necrosis in the epidermis upto 5 min although moderate changes were observed at 30 min. Pretreated samples were analyzed for detection of reaction products with m/z value of 75.04, 69.08, 83.93, 85.95, 123.99, 126.00, and 108.97. HOCl showed a strong bactericidal effect at 40 ppm. The absorbance spectra of HOCl treated CEES showed lowered peaks in comparison to CEES alone and other oxidizing agents. Conclusion: In a nutshell, our results signify the decontamination role of HOCl for biological surface application.

Background: Pre-operative autologous blood donation (PABD) is one of the most widely distributed autologous blood donation means, which has positive effects on erythropoiesis. However, whether PABD can stimulate the bone marrow hematopoiesis after hepatectomy has not been reported. Methods: Totally 80 New Zealand rabbits were randomly divided into 4 groups that included control group, surgery group, hemodilutional autotransfusion (HA) group and PABD group. Automatic reticulocyte examination was performed to detect the content of reticulocyte and immature reticulocyte fractions (IRF). Flow cytometric analysis was employed to monitor the level of CD34+ cells and the cell cycle status. Southern blotting was conducted to determine the telomere length of CD34+ cells. Results: The content of high fluorescence reticulocytes (HFR) and IRF was decreased at 6 h and 24 h after autotransfusion. However, the level of CD34+ cells was upregulated after PABD. Cell cycle status analysis revealed that the majority of the CD34+ cells in HA and PABD group were maintained in G0/G1 phase. The telomere length in HA and PABD group was shortened than that of the control group and surgery group. Conclusion: PABD could promote the bone marrow hematopoietic functions in rabbits after hepatectomy via stimulating proliferation of CD34+ cells and shortening the telomere length of CD34+ cells, but the content of HFR was not increased immediately because of the stuck of CD34+ cells in the G0/G1 phase.

Exposure to environmental toxicants such as Arsenic (As) can result in As-induced alterations in immune regulators. Consequently, people who are more prone to viral infections like influenza A or B, H1N1, SARS CoV (Severe Acute Respiratory Syndrome Coronavirus), and SARS CoV2 may develop a susceptibility to immune responses in their lungs because our previous reports delineated the ability of QIAPI 1^®, a melanin precursor, to dissociate water molecules with simultaneous therapeutic efficacy against central nervous system (CNS) diseases, retinopathy, and As-induced renal toxicity. Considering the commonalities of lung pathology of SARS CoV and As-induced toxicity, the aim of this study is to decipher the efficacy of QIAPI 1^® against pentavalent As-induced lung toxicity by examining the pulmonary pathology. Hematoxylin & Eosin (H&E) staining was used for ascertaining the lung pathology in Wistar rat models. Animals were divided into 3 groups: control group, group treated with pentavalent As, and a group treated with pentavalent As and QIAPI 1^®. There were no significant changes in lung histopathology in the control group as indicated by intact morphology. The As-treated group revealed damage to the histoarchitecture with pulmonary edema, interstitial fibrosis, diffuse alveolar damage, Bronchiolitis obliterans organizing pneumonia (BOOP)-lesions, formation of hyaline membrane, multinucleated giant pneumocytes, atypical pneumocytes, inflammatory cell infiltration, and interstitial edema. The group treated with As and QIAPI 1^® significantly associated with mitigated histological signs of lung inflammation induced by Arsenic. Therefore, QIAPI 1^® can be recommended as antagonistic to Asinduced lung toxicity. In conclusion, this model could be preferred as a hypothetical model to examine the efficacy of QIAPI 1^® in SARS CoV2-induced pulmonary damage. Future studies are warranted to delineate the efficacy of QIAPI 1® against SARS CoV and SARS CoV2 lung pathology.