Recent advancements in nanomaterial-mediated ferroptosis-induced cancer therapy: Importance of molecular dynamics and novel strategies.

Ferroptosis is a novel type of controlled cell death resulting from an imbalance between oxidative harm and protective mechanisms, demonstrating significant potential in combating cancer. It differs from other forms of cell death, such as apoptosis and necrosis. Molecular therapeutics have hard time playing the long-acting role of ferroptosis induction due to their limited water solubility, low cell targeting capacity, and quick metabolism in vivo. To this end, small molecule inducers based on biological factors have long been used as strategy to induce cell death. Research into ferroptosis and advancements in nanotechnology have led to the discovery that nanomaterials are superior to biological medications in triggering ferroptosis. Nanomaterials derived from iron can enhance ferroptosis induction by directly releasing large quantities of iron and increasing cell ROS levels. Moreover, utilizing nanomaterials to promote programmed cell death minimizes the probability of unfavorable effects induced by mutations in cancer-associated genes such as RAS and TP53. Taken together, this review summarizes the molecular mechanisms involved in ferroptosis along with the classification of ferroptosis induction. It also emphasized the importance of cell organelles in the control of ferroptosis in cancer therapy. The nanomaterials that trigger ferroptosis are categorized and explained. Iron-based and noniron-based nanomaterials with their characterization at the molecular and cellular levels have been explored, which will be useful for inducing ferroptosis that leads to reduced tumor growth. Within this framework, we offer a synopsis, which traverses the well-established mechanism of ferroptosis and offers practical suggestions for the design and therapeutic use of nanomaterials.

Pharmacological Insights: Mitochondrial ROS Generation by FNC (Azvudine) in Dalton's Lymphoma Cells Revealed by Super Resolution Imaging.

Nucleoside analogs are a common form of chemotherapy that disrupts DNA replication and repair, leading to cell cycle arrest and apoptosis. Reactive oxygen species (ROS) production is a significant mechanism through which these drugs exert their anticancer effects. This study investigated a new nucleoside analog called FNC or Azvudine, and its impact on ROS production and cell viability in Dalton's lymphoma (DL) cells. The study found that FNC treatment resulted in a time- and dose-dependent increase in ROS levels in DL cells. After 15 and 30 min of treatment with 2 and 1 mg/ml of FNC, mitochondrial ROS production was observed in DL cells. Furthermore, prolonged exposure to FNC caused structural alterations and DNA damage in DL cells. The results suggest that FNC's ability to impair DL cell viability may be due to its induction of ROS production and indicate a need for further investigation.

Mitochondrial-mediated apoptosis as a therapeutic target for FNC (2'-deoxy-2'-b-fluoro-4'-azidocytidine)-induced inhibition of Dalton's lymphoma growth and proliferation.

PURPOSE: T-cell lymphomas, refer to a diverse set of lymphomas that originate from T-cells, a type of white blood cell, with limited treatment options. This investigation aimed to assess the efficacy and mechanism of a novel fluorinated nucleoside analogue (FNA), 2'-deoxy-2'-ß-fluoro-4'-azidocytidine (FNC), against T-cell lymphoma using Dalton's lymphoma (DL)-bearing mice as a model. METHODS: Balb/c mice transplanted with the DL tumor model received FNC treatment to study therapeutic efficacy against T-cell lymphoma. Behavioral monitoring, physiological measurements, and various analyses were conducted to evaluate treatment effects for mechanistic investigations. RESULTS: The results of study indicated that FNC prevented DL-altered behavior parameters, weight gain and alteration in organ structure, hematological parameters, and liver enzyme levels. Moreover, FNC treatment restored organ structures, attenuated angiogenesis, reduced DL cell viability and proliferation through apoptosis. The mechanism investigation revealed FNC diminished MMP levels, induced apoptosis through ROS induction, and activated mitochondrial-mediated pathways leading to increase in mean survival time of DL mice. These findings suggest that FNC has potential therapeutic effects in mitigating DL-induced adverse effects. CONCLUSION: FNC represents an efficient and targeted treatment strategy against T-cell lymphoma. FNC's proficient ability to induce apoptosis through ROS generation and MMP reduction makes it a promising candidate for developing newer and more effective anticancer therapies. Continued research could unveil FNC's potential role in designing a better therapeutic approach against NHL.

FNC (4'-azido-2'-deoxy-2'-fluoro(arbino)cytidine) as an Effective Therapeutic Agent for NHL: ROS Generation, Cell Cycle Arrest, and Mitochondrial-Mediated Apoptosis.

Cytotoxic nucleoside analogs (NAs) hold great promise in cancer therapeutics by mimicking endogenous nucleosides and interfering with crucial cellular processes. Here, we investigate the potential of the novel cytidine analog, 4'-azido-2'-deoxy-2'-fluoro(arbino)cytidine (FNC), as a therapeutic agent for Non-Hodgkin lymphoma (NHL) using Dalton's lymphoma (DL) as a T-cell lymphoma model. FNC demonstrated dose- and time-dependent inhibition of DL cell growth and proliferation. IC-50 values of FNC were measured at 1 µM, 0.5 µM, and 0.1 µM after 24, 48, and 72 h, respectively. Further elucidation of FNC's mechanism of action uncovers its role in inducing apoptosis in DL cells. Notable DNA fragmentation and nuclear condensation point to activated apoptotic pathways. FNC-induced apoptosis was concomitant with changes in cellular membranes, characterized by membrane rupture and altered morphology. The robust anticancer effects of FNC are linked to its capacity to induce reactive oxygen species (ROS) production, prompting oxidative stress-mediated apoptosis. Additionally, FNC disrupted mitochondrial membrane potential (MMP), leading to mitochondrial dysfunction, further promoting apoptosis. Dysregulation of apoptotic genes, with upregulation of Bax and downregulation of Bcl-2 and Bcl-xl, implicates the mitochondrial-mediated apoptosis pathway. Furthermore, FNC-induced G2/M phase cell cycle arrest was mediated through modulation of the cell cycle inhibitor p21. Overall, this study highlights the potential of FNC as a promising therapeutic agent for NHL.

XLG2 and CORI3 function additively to regulate plant defense against the necrotrophic pathogen Sclerotinia sclerotiorum.

The membrane-bound heterotrimeric G-proteins in plants play a crucial role in defending against a broad range of pathogens. This study emphasizes the significance of Extra-large Gα protein 2 (XLG2), a plant-specific G-protein, in mediating the plant response to Sclerotinia sclerotiorum, which infects over 600 plant species worldwide. Our analysis of Arabidopsis G-protein mutants showed that loss of XLG2 function increased susceptibility to S. sclerotiorum, accompanied by compromised accumulation of jasmonic acid (JA) during pathogen infection. Overexpression of the XLG2 gene in xlg2 mutant plants resulted in higher resistance and increased JA accumulation during S. sclerotiorum infection. Co-immunoprecipitation (co-IP) analysis on S. sclerotiorum infected Col-0 samples, using two different approaches, identified 201 XLG2-interacting proteins. The identified JA-biosynthetic and JA-responsive proteins had compromised transcript expression in the xlg2 mutant during pathogen infection. XLG2 was found to interact physically with a JA-responsive protein, Coronatine induced 1 (CORI3) in Co-IP, and confirmed using split firefly luciferase complementation and bimolecular fluorescent complementation assays. Additionally, genetic analysis revealed an additive effect of XLG2 and CORI3 on resistance against S. sclerotiorum, JA accumulation, and expression of the defense marker genes. Overall, our study reveals two independent pathways involving XLG2 and CORI3 in contributing resistance against S. sclerotiorum.

Expanded therapeutic applications of Holarrhena antidysenterica: A review.

BACKGROUND: The use of medicinal plants as a rich resource of therapeutic agents in the treatment and prevention of diseases & ailments has been recognized for millennia and is highly regarded worldwide. Holarrhena antidysenterica (H. antidysenterica), also called kurchi, or kutaj, has been utilized since the dawn of time, Apocynaceae member, also known as H. pubescens, is praised for the medicinal uses of its stem bark, leaves, and seeds in Ayurveda. OBJECTIVE: The study concentrated on aggregate information regarding H. antidysenterica's therapeutic effects. The purpose of this study was to determine the antidiabetic activity of an extract from H. antidysenterica seeds in diabetic rats induced by streptozotocin. METHODS: Regardless of its broad variety of biological and possible therapeutic uses, there has been increasing concern regarding the use of H. antidysenterica. RESULT: Various phytochemicals have been extracted from H. antidysenterica in recent years and have demonstrated typical pharmacological properties, including antibacterial, anti-diarrhoeal, anti-diabetic, anti-oxidant, anti-urolithic, and anti-inflammatory activity.. CONCLUSION: This review paper investigated the in-depth description and pharmacological properties of the plant, which produced significant findings on the chemical components present and also verified the traditionally claimed properties associated with the plant.

Therapeutic and Phytochemical Properties of Thymoquinone Derived from Nigella Sativa.

BACKGROUND: Nigella sativa (N. sativa), commonly known as black seed or black cumin, belongs to the family Ranunculaceae. It contains several phytoconstituents, thymoquinone (TQ), thymol, thymohydroquinone, carvacrol, and dithymoquinone. TQ is the main phytoconstituent present in N. sativa that is used as an herbal compound, and it is widely used as an antihypertensive, liver tonic, diuretic, digestive, anti-diarrheal, appetite stimulant, analgesic, and antibacterial agent, and in skin disorders. OBJECTIVE: The study focused on collecting data on the therapeutic or pharmacological activities of TQ present in N. sativa seed. METHODS: Antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, antiinflammatory, hepato-protective, renal protective, and antioxidant properties of TQ have been studied by various scientists. CONCLUSION: TQ seems to have a variety of consequences on how infected cells behave at the cellular level.

Safety Assessment of a Nucleoside Analogue FNC (2'-deoxy-2'- ß-fluoro-4'-azidocytidine ) in Balb/c Mice: Acute Toxicity Study.

OBJECTIVES: The present study aimed to provide an insight into the acute toxicity of a novel fluorinated nucleoside analogue (FNA), FNC (Azvudine or2'-deoxy-2'-ß-fluoro-4'-azidocytidine). FNC showed potent anti-viral and anti-cancer activities and approved drug for high-load HIV patients, despite, its acute toxicity study being lacking. MATERIALS AND METHODS: OECD-423 guidelines were followed during this study and the parameters were divided into four categories - behavioral parameters, physiological parameters, histopathological parameters, and supplementary tests. The behavioral parameters included feeding, body weight, belly size, organ weight and size, and mice behavior. The physiological parameters consisted of blood, liver, and kidney indicators. In histopathological parameters hematoxylin and eosin staining was performed to analyse the histological changes in the mice organs after FNC exposure. In addition, supplementary tests were conducted to assess cellular viability, DNA fragmentation and cytokine levels (IL-6 and TNF-α) in response to FNC. RESULTS: In the behavioral parameters FNC induced changes in the mice-to-mice interaction and activities. Mice's body weight, belly size, organ weight, and size remained unchanged. Physiological parameters of blood showed that FNC increased the level of WBC, RBC, Hb, and neutrophils and decreased the % count of lymphocytes. Liver enzymes SGOT (AST), and ALP was increased. In the renal function test (RFT) cholesterol level was significantly decreased. Histopathological analysis of the liver, kidney, brain, heart, lungs, and spleen showed no sign of tissue damage at the highest FNC dose of 25 mg/kg b.wt. Supplementary tests for cell viability showed no change in viability footprint, through our recently developed dilution cum-trypan (DCT) assay, and Annexin/PI. No DNA damage or apoptosis was observed in DAPI or AO/EtBr studies. Pro-inflammatory cytokines IL-6 and TNF-α increased in a dose-dependent manner. CONCLUSION: This study concluded that FNC is safe to use though higher concentration shows slight toxicity.

Pharmaceutical Considerations of Translabial Formulations for Treatment of Parkinson's Disease: A Concept of Drug Delivery for Unconscious Patients.

PURPOSE: The goal of the present research was to isolate a biopolymer from Phaseolus vulgaris (P. vulgaris) and Zea mays (Z. mays) plants and used it to construct Resveratrol (RES)-loaded translabial films. METHODS: Biopolymers were extracted from P. vulgaris and Z. mays seeds using a simple process. Separated biopolymers, sodium carboxymethylcellulose (SCMC) and tragacanth were subjected to formulation development by incorporating RES-loaded translabial films. The Fourier-transform infrared spectroscopy (FTIR), physical appearance, weight, thickness, folding endurance, swelling index, surface pH, percent moisture absorption, percent moisture loss, vapor transfer rate, and content uniformity of the translabial films were examined. The mucoadhesive, ex-vivo permeation, in vivo and stability studies, were performed. RESULTS: The results showed that RES-loaded translabial films produced from P. vulgaris and Z. mays biopolymers exhibited exceptional mucoadhesive, stability, and permeation properties. Results revealed that the best formulations were prepared from a combination of biopolymer (P. vulgaris C or Z. mays C) with tragacanth. Formulations with tragacanth revealed good swelling and thus permeation profiles. In vivo release of TL 11 was found to be 24.05 ng/ml in 10 hours and it was stable enough at 45°C. CONCLUSION: This research suggested that RES-loaded translabial formulations can be potentially used for the treatment of Parkinson's disease with good patient compliance to geriatric and unconscious patients.

Demand creation for HIV testing services: A systematic review and meta-analysis.

BACKGROUND: HIV testing services (HTS) are the first steps in reaching the UNAIDS 95-95-95 goals to achieve and maintain low HIV incidence. Evaluating the effectiveness of different demand creation interventions to increase uptake of efficient and effective HTS is useful to prioritize limited programmatic resources. This review was undertaken to inform World Health Organization (WHO) 2019 HIV testing guidelines and assessed the research question, "Which demand creation strategies are effective for enhancing uptake of HTS?" focused on populations globally. METHODS AND FINDINGS: The following electronic databases were searched through September 28, 2021: PubMed, PsycInfo, Cochrane CENTRAL, CINAHL Complete, Web of Science Core Collection, EMBASE, and Global Health Database; we searched IAS and AIDS conferences. We systematically searched for randomized controlled trials (RCTs) that compared any demand creation intervention (incentives, mobilization, counseling, tailoring, and digital interventions) to either a control or other demand creation intervention and reported HTS uptake. We pooled trials to evaluate categories of demand creation interventions using random-effects models for meta-analysis and assessed study quality with Cochrane's risk of bias 1 tool. This study was funded by the WHO and registered in Prospero with ID CRD42022296947. We screened 10,583 records and 507 conference abstracts, reviewed 952 full texts, and included 124 RCTs for data extraction. The majority of studies were from the African (N = 53) and Americas (N = 54) regions. We found that mobilization (relative risk [RR]: 2.01, 95% confidence interval [CI]: [1.30, 3.09], p < 0.05; risk difference [RD]: 0.29, 95% CI [0.16, 0.43], p < 0.05, N = 4 RCTs), couple-oriented counseling (RR: 1.98, 95% CI [1.02, 3.86], p < 0.05; RD: 0.12, 95% CI [0.03, 0.21], p < 0.05, N = 4 RCTs), peer-led interventions (RR: 1.57, 95% CI [1.15, 2.15], p < 0.05; RD: 0.18, 95% CI [0.06, 0.31], p < 0.05, N = 10 RCTs), motivation-oriented counseling (RR: 1.53, 95% CI [1.07, 2.20], p < 0.05; RD: 0.17, 95% CI [0.00, 0.34], p < 0.05, N = 4 RCTs), short message service (SMS) (RR: 1.53, 95% CI [1.09, 2.16], p < 0.05; RD: 0.11, 95% CI [0.03, 0.19], p < 0.05, N = 5 RCTs), and conditional fixed value incentives (RR: 1.52, 95% CI [1.21, 1.91], p < 0.05; RD: 0.15, 95% CI [0.07, 0.22], p < 0.05, N = 11 RCTs) all significantly and importantly (≥50% relative increase) increased HTS uptake and had medium risk of bias. Lottery-based incentives and audio-based interventions less importantly (25% to 49% increase) but not significantly increased HTS uptake (medium risk of bias). Personal invitation letters and personalized message content significantly but not importantly (<25% increase) increased HTS uptake (medium risk of bias). Reduced duration counseling had comparable performance to standard duration counseling (low risk of bias) and video-based interventions were comparable or better than in-person counseling (medium risk of bias). Heterogeneity of effect among pooled studies was high. This study was limited in that we restricted to randomized trials, which may be systematically less readily available for key populations; additionally, we compare only pooled estimates for interventions with multiple studies rather than single study estimates, and there was evidence of publication bias for several interventions. CONCLUSIONS: Mobilization, couple- and motivation-oriented counseling, peer-led interventions, conditional fixed value incentives, and SMS are high-impact demand creation interventions and should be prioritized for programmatic consideration. Reduced duration counseling and video-based interventions are an efficient and effective alternative to address staffing shortages. Investment in demand creation activities should prioritize those with undiagnosed HIV or ongoing HIV exposure. Selection of demand creation interventions must consider risks and benefits, context-specific factors, feasibility and sustainability, country ownership, and universal health coverage across disease areas.

Insights into genomic variations in rice Hsp100 genes across diverse rice accessions.

MAIN CONCLUSION: The Hsp101 gene is present across all sequenced rice genomes. However, as against Japonica rice, Hsp101 protein of most indica and aus rice contain insertion of glutamic acid at 907th position. The understanding of the heat stress response of rice plants is important for worldwide food security. We examined the presence/absence variations (PAVs) of heat shock proteins (Hsps)/heat shock transcription factor (Hsf) genes in cultivated rice accessions. While 53 Hsps/Hsfs genes showed variable extent of PAVs, 194 genes were the core genes present in all the rice accessions. ClpB1/Hsp101 gene, which is critically important for thermotolerance in plants, showed 100% distribution across the rice types. Within the ClpB1 gene sequence, 40 variation sites consisting of nucleotide polymorphisms (SNPs) and short insertion/deletions (InDels) were discerned. An InDel in ClpB1 leading to an in-frame insertion of 3 nucleotides (TCC) thereby an additional amino acid (glutamic acid) at 907th amino acid position was noted in most of the indica and aus as against japonica rice types. Three rice types namely Moroberekan (japonica), IR64 (indica) and N22 (aus) were further analyzed to address the question of ClpB1 genomic variations and its protein levels with the heat tolerance phenotype. The growth profiling analysis in the post heat stress (HS) period showed that N22 seedlings were most tolerant, IR64 moderately tolerant and Moroberekan highly sensitive. Importantly, the ClpB1 protein sequences of these three rice types showed distinct differences in terms of SNPs. As the ClpB1 protein levels accumulated post HS were generally higher in Moroberekan than N22 seedlings in our study, it is proposed that some additional gene loci in conjunction with ClpB1 regulate the overall rice heat stress response.

Local Drug Delivery Strategies towards Wound Healing.

A particular biological process known as wound healing is connected to the overall phenomena of growth and tissue regeneration. Several cellular and matrix elements work together to restore the integrity of injured tissue. The goal of the present review paper focused on the physiology of wound healing, medications used to treat wound healing, and local drug delivery systems for possible skin wound therapy. The capacity of the skin to heal a wound is the result of a highly intricate process that involves several different processes, such as vascular response, blood coagulation, fibrin network creation, re-epithelialisation, collagen maturation, and connective tissue remodelling. Wound healing may be controlled with topical antiseptics, topical antibiotics, herbal remedies, and cellular initiators. In order to effectively eradicate infections and shorten the healing process, contemporary antimicrobial treatments that include antibiotics or antiseptics must be investigated. A variety of delivery systems were described, including innovative delivery systems, hydrogels, microspheres, gold and silver nanoparticles, vesicles, emulsifying systems, nanofibres, artificial dressings, three-dimensional printed skin replacements, dendrimers and carbon nanotubes. It may be inferred that enhanced local delivery methods might be used to provide wound healing agents for faster healing of skin wounds.

An Exploration of Herbal Extracts Loaded Phyto-phospholipid Complexes (Phytosomes) Against Polycystic Ovarian Syndrome: Formulation Considerations.

BACKGROUND: Herbal preparations with low oral bioavailability have a fast first-pass metabolism in the gut and liver. To offset these effects, a method to improve absorption and, as a result, bioavailability must be devised. OBJECTIVE: The goal of this study was to design, develop, and assess the in vivo toxicity of polyherbal phytosomes for ovarian cyst therapy. METHODS: Using antisolvent and rotational evaporation procedures, phytosomes containing phosphatidylcholine and a combination of herbal extracts (Saraca asoca, Bauhinia variegata, and Commiphora mukul) were synthesized. For a blend of Saraca asoca, Bauhinia variegata, and Commiphora mukul, Fourier-transform infrared spectroscopy (FTIR), preformulation investigations, qualitative phytochemical screening, and UV spectrophotometric tests were conducted. Scanning electron microscopy (SEM), zeta potential, ex vivo release, and in vivo toxicological investigations were used to examine phytosomes. RESULTS: FTIR studies suggested no changes in descriptive peaks in raw and extracted herbs, although the intensity of peaks was slightly reduced. Zeta potential values between -20.4 mV to - 29.6 mV suggested stable phytosomes with an accepted particle size range. Percentage yield and entrapment efficiency were directly correlated to the amount of phospholipid used. Ex vivo studies suggested that the phytosomes with low content of phospholipids showed good permeation profiles. There was no difference in clinical indications between the extract-loaded phytosomes group and the free extract group in in vivo toxicological or histopathological examinations. CONCLUSION: The findings of current research work suggested that the optimized phytosomes based drug delivery containing herbal extracts as bioenhancers has the potential to improve the bioavailability of hydrophobic extracts.

Preventive and Therapeutic Aspects of Migraine for Patient Care: An Insight.

BACKGROUND: Migraine is a common neurological condition marked by frequent mild to extreme headaches that last 4 to 72 hours. A migraine headache may cause a pulsing or concentrated throbbing pain in one part of the brain. Nausea, vomiting, excessive sensitivity to light and sound, smell, feeling sick, vomiting, painful headache, and blurred vision are all symptoms of migraine disorder. Females are more affected by migraines in comparison to males. OBJECTIVE: The present review article summarizes preventive and therapeutic measures, including allopathic and herbal remedies for the treatment of migraine. RESULTS: This review highlights the current aspects of migraine pathophysiology and covers an understanding of the complex workings of the migraine state. Therapeutic agents that could provide an effective treatment have also been discussed. CONCLUSION: It can be concluded that different migraines could be treated based on their type and severity.

Physiological and Pathophysiological Aspects of Diabetic Foot Ulcer and its Treatment Strategies.

BACKGROUND: Diabetes foot ulcers (DFU) are among the most common complications in diabetic patients, leading to amputation and psychological distress. This mini-review covers the general physiology of ulcer healing as well as the pathophysiology of DFU and its therapies. Only a few treatments have been sanctioned and numerous compounds from various pharmacological groups are now being tested at various stages for the prevention and treatment of DFUs. OBJECTIVE: The main objective of this mini-review is to give concise information on how diabetes mellitus impairs the healing of chronic ulcers by disrupting numerous biological systems of the normal healing process, resulting in diabetic foot ulceration, and the current therapeutic approaches. METHODS: A review of accessible material from systemic searches in the PubMed/Medline, Scopus, Cochrane Database of Systematic Reviews, published review articles, and Clinical Trials databases (US National Library of Medicine) with no period of limitation was conducted. RESULTS: The treatment of DFUs comprises wound dressings, use of matrix metalloproteinase inhibitors in wound dressing, antibiotics, skin substitutes, pressure off-loading growth factors and stem cells, gene therapy, topical oxygen therapy, etc. Conclusion: The majority of these treatments are aimed at treating diabetic foot ulcers and preventing diabetic wounds from becoming infected. Yet, there is no single therapy that can be advised for diabetic foot ulcer patients. Future treatment strategies should be considered an appropriate treatment option for persistent wounds.

Nrf2 Mediated Heme Oxygenase-1 Activation Contributes to Diabetic Wound Healing - an Overview.

Diabetic wound healing is a complicated procedure because hyperglycemia changes the various stages of wound healing. In type 2 diabetes mellitus (T2DM), oxidative stress is proven to be a critical factor in causing non-healing wounds and aggravating the inflammatory phase, resulting in the amputation of lower limbs in T2DM patients. This makes scientists figure out how to control oxidative stress and chronic inflammation at the molecular level. Nuclear factor erythroid 2- related factor 2 (Nrf2) releases antioxidant proteins to suppress reactive oxygen species (ROS) activation and inflammation. The current review discusses the role of Nrf2 in improving diabetic wound healing by reducing the production of ROS and thus reducing oxidative stress, as well as inhibiting nuclear factor kappa B (NF-kB) dissociation and nuclear translocation, which prevents the release of inflammatory mediators and increases antioxidant protein levels, thereby improving diabetic wound healing. As a result, the researcher will be able to find a more effective diabetic wound healing therapy.

Swine coronaviruses (SCoVs) and their emerging threats to swine population, inter-species transmission, exploring the susceptibility of pigs for SARS-CoV-2 and zoonotic concerns.

Swine coronaviruses (SCoVs) are one of the most devastating pathogens affecting the livelihoods of farmers and swine industry across the world. These include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine respiratory coronavirus (PRCV), porcine hemagglutinating encephalomyelitis virus (PHEV), swine acute diarrhea syndrome coronavirus (SADS-CoV), and porcine delta coronavirus (PDCoV). Coronaviruses infect a wide variety of animal species and humans because these are having single stranded-RNA that accounts for high mutation rates and thus could break the species barrier. The gastrointestinal, cardiovascular, and nervous systems are the primary organ systems affected by SCoVs. Infection is very common in piglets compared to adult swine causing high mortality in the former. Bat is implicated to be the origin of all CoVs affecting animals and humans. Since pig is the only domestic animal in which CoVs cause a wide range of diseases; new coronaviruses with high zoonotic potential could likely emerge in the future as observed in the past. The recently emerged severe acute respiratory syndrome coronavirus virus-2 (SARS-CoV-2), causing COVID-19 pandemic in humans, has been implicated to have animal origin, also reported from few animal species, though its zoonotic concerns are still under investigation. This review discusses SCoVs and their epidemiology, virology, evolution, pathology, wildlife reservoirs, interspecies transmission, spill-over events and highlighting their emerging threats to swine population. The role of pigs amid ongoing SARS-CoV-2 pandemic will also be discussed. A thorough investigation should be conducted to rule out zoonotic potential of SCoVs and to design appropriate strategies for their prevention and control.

Biochanin-A: A Bioactive Natural Product with Versatile Therapeutic Perspectives.

BACKGROUND: Biochanin-A (5,7 dihydroxy 4 methoxy isoflavone) is a phytochemical phytoestrogen that is highly effective against various diseases. Biochanin-A is a nutritional and dietary isoflavonoid naturally present in red clover, chickpea, soybeans and other herbs. Biochanin- A possesses numerous biological activities. OBJECTIVE: The study focused on collective data of therapeutic activities of Biochanin-A. METHODS: According to the literature, biochanin-A revealed a range of activities starting from chemoprevention, by hindering cell growth, activation of tumor cell death, hampering metastasis, angiogenic action, cell cycle regulation, neuroprotection, by controlling microglial activation, balancing antioxidants, elevating the neurochemicals, suppressing BACE-1, NADPH oxidase hindrance to inflammation, by mitigating the MAPK and NF- κB, discharge of inflammatory markers, upregulating the PPAR-γ, improving the function of heme oxygenase-1, erythroid 2 nuclear factors, detoxifying the oxygen radicals and stimulating the superoxide dismutase action, and controlling its production of transcription factors. Against pathogens, biochanin-A acts by dephosphorylating tyrosine kinase proteins, obstructing gram-negative bacteria, suppressing the development of cytokines from viruses, and improving the action of a neuraminidase cleavage of caspase-3, and acts as an efflux pump inhibitor. In metabolic disorders, biochanin-A acts by encouraging transcriptional initiation and inhibition, activating estrogen receptors, and increasing the activity of differentiation, autophagy, inflammation, and blood glucose metabolism. CONCLUSION: Therefore, biochanin-A could be used as a therapeutic drug for various pathological conditions and treatments in human beings.

Need of booster vaccine doses to counteract the emergence of SARS-CoV-2 variants in the context of the Omicron variant and increasing COVID-19 cases: An update.

The emergence of different variants of SARS-CoV-2, including the Omicron (B.1.1.529) variant in November 2021, has resulted in a continuous major health concern at a global scale. Presently, the Omicron variant has spread very rapidly worldwide within a short time period. As the most mutated variant of SARS-CoV-2, Omicron has instilled serious uncertainties on the effectiveness of humoral adaptive immunity generated by COVID-19 vaccination or an active viral infection as well as the protection provided by antibody-based immunotherapies. Amidst such high public health concerns, the need to carry out booster vaccination has been emphasized. Current evidence reveals the importance of incorporating booster vaccination using several vaccine platforms, such as viral vector- and mRNA-based vaccines, as well as other platforms that are under explorative investigations. Further research is being conducted to assess the effectiveness and durability of protection provided by booster COVID-19 vaccination against Omicron and other SARS-CoV-2 variants.

Advancements in cell membrane camouflaged nanoparticles: A bioinspired platform for cancer therapy.

The idea of employing natural cell membranes as a coating medium for nanoparticles (NPs) endows man-made vectors with natural capabilities and benefits. In addition to retaining the physicochemical characteristics of the NPs, the biomimetic NPs also have the functionality of source cell membranes. It has emerged as a promising approach to enhancing the properties of NPs for drug delivery, immune evasion, imaging, cancer-targeting, and phototherapy sensitivity. Several studies have been reported with a multitude of approaches to reengineering the surface of NPs using biological membranes. Owing to their low immunogenicity and intriguing biomimetic properties, cell-membrane-based biohybrid delivery systems have recently gained a lot of interest as therapeutic delivery systems. This review summarises different kinds of biomimetic NPs reported so far, their fabrication aspects, and their application in the biomedical field. Finally, it briefs on the latest advances available in this biohybrid concept.