Toxicological evaluation of therapeutically active zinc oxide nanoflowers in pre-clinical mouse model.

Our earlier reports established that zinc oxide nanoflowers (ZONF) show significant pro-angiogenic properties, where reactive oxygen species, nitric oxide and MAPK-AKT-eNOS cell signaling axis play an essential task. Considering the significance of angiogenesis in healthcare, our research group has recently demonstrated the in vivo therapeutic application of ZONF (10 mg/kg b.w.

Biochanin-A attenuates DHEA-induced polycystic ovary syndrome via upregulation of GDF9 and BMP15 signaling in vivo.

Aims: Phytoestrogens can act as natural estrogens owing to their structural similarity to human estrogens. Biochanin-A (BCA) is a well-studied phytoestrogen with a wide variety of pharmacological activities, whereas not reported in the most frequently encountered endocrinopathy called polycystic ovary syndrome (PCOS) in women.

Purpose: This study aimed to investigate the therapeutic effect of BCA on dehydroepiandrosterone (DHEA) induced PCOS in mice.

Combination treatment of recombinant growth differentiation factor-9 and Cetrorelix improves gestational origin of the polycystic ovarian syndrome in female rats.

Aims: Polycystic ovary syndrome (PCOS) is a hyper-androgenic endocrinopathy prevalent in premenopausal women with no cure available. The current study aimed to investigate the therapeutic effect of recombinant GDF-9 and Cetrorelix on the gestational origin of dehydroepiandrosterone (DHEA) induced PCOS in postnatal pups' delivered to rat dams.

Main Methods: The body weight measurement, blood and serum analysis for glucose tolerance, lipid profile, liver enzymes, sex hormones (Testosterone, Estradiol, and Progesterone), estrus cyclicity assessment, histological staining of ovary and liver, molecular markers expressions of pro-inflammatory by qRT-PCR and immuno-histochemistry technique for folliculogenesis genes and histological staining studies of liver and ovary were done.

Sinigrin Attenuates the Dextran Sulfate Sodium-induced Colitis in Mice by Modulating the MAPK Pathway.

Ulcerative colitis (UC) is an intestinal inflammatory disease characterised by the loss of intestinal crypts, edema, mucosal ulceration, and infiltration of inflammatory cells in the mucosa. The current study aimed to investigate the protective and therapeutic effects of sinigrin and underlying mechanisms in a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis. DSS-induced colitis models were used to demonstrate sinigrin's therapeutic/protective action.

Long-term and non-invasive tracking of DiD dye-labeled human hepatic progenitors in chronic liver disease models.

Background: Chronic liver diseases (CLD) are the major public health burden due to the continuous increasing rate of global morbidity and mortality. The inherent limitations of organ transplantation have led to the development of stem cell-based therapy as a supportive and promising therapeutic option. However, identifying the fate of transplanted cells represents a crucial obstacle.

Mitochondria-targeted esculetin mitigates atherosclerosis in the setting of aging via the modulation of SIRT1-mediated vascular cell senescence and mitochondrial function in Apoe mice.

Background And Aims: Age is a dominant and independent risk factor for the development of atherosclerosis, a major cardiovascular disease, and if left untreated leads to myocardial infarction and death. Mitochondria-targeted anti-oxidants are evolving as a new class of compounds that can alter the pathophysiology of age-related diseases, including atherosclerosis, where mitochondrial dysfunction plays a critical role in disease progression.

Methods: We recently synthesized an alkyl TPP + -tagged esculetin (mitochondria-targeted esculetin or Mito-Esc).

Equine immunoglobulin fragment F(ab') displays high neutralizing capability against multiple SARS-CoV-2 variants.

Neutralizing antibody-based passive immunotherapy could be an important therapeutic option against COVID-19. Herein, we demonstrate that equines hyper-immunized with chemically inactivated SARS-CoV-2 elicited high antibody titers with a strong virus-neutralizing potential, and F(ab') fragments purified from them displayed strong neutralization potential against five different SARS-CoV-2 variants. F(ab') fragments purified from the plasma of hyperimmunized horses showed high antigen-specific affinity.

Dehydrozingerone ameliorates Lipopolysaccharide induced acute respiratory distress syndrome by inhibiting cytokine storm, oxidative stress via modulating the MAPK/NF-κB pathway.

Background: Inflammation-mediated lung injury is a major cause of health problems in many countries and has been the leading cause of morbidity/mortality in intensive care units. In the current COVID-19 pandemic, the majority of the patients experienced serious pneumonia resulting from inflammation (Acute respiratory distress syndrome/ARDS). Pathogenic infections cause cytokine release syndrome (CRS) by hyperactivation of immune cells, which in turn release excessive cytokines causing ARDS.

Galangin ameliorates Imiquimod-Induced psoriasis-like skin inflammation in BALB/c mice via down regulating NF-κB and activation of Nrf2 signaling pathways.

Psoriasis is a most common chronic autoimmune-arbitrated cutaneous inflammatory skin disorder by unclear pathogenesis. In this current study we demonstrated the effect of galangin (GAL) on imiquimod (IMQ)-induced psoriasis-like skin inflammation and decipher its possible protective mechanism which has not been investigated. The in vivo results revealed that GAL at 1% w/w and 2% w/w for six consecutive days markedly reduced IMQ-induced PASI scoring, skin, ear thickness, hematological markers, levels of nitrites, TBARS, MPO, histopathological, as well modulated the protein levels of pro-inflammatory mediators of COX-2, iNOS, NF-κB pathway and pro-inflammatory cytokines IL-17, IL-23, IL-1β in the skin and also IL-6, TNF-α in both skin and serum.

Fluorinated thiazolidinol drives autophagic cell death in pancreatic cancer cells via AMPK activation and perturbation of critical sentinels of oncogenic signaling.

Pancreatic cancer is one of the most malignant cancers around the world. The co-occurrence of mutation in KRAS and p53 makes it highly aggressive, proliferative, metastatic, and resistant to apoptotic cell death. Therefore, there is a need to trigger an alternate mechanism of cancer cell death in apoptosis-resistant pancreatic cancer.

Ag[Fe(CN)NO]-Fabricated Hydrophobic Cotton as a Potential Wound Healing Dressing: An Approach.

There have been reports of different types of wound dressings for various functions and purposes. Cotton being one of the most widely used wound dressing material due to its non-toxic, biodegradable, and other properties is used for fabrication as well as in the form of scaffolds for faster and effective wound closure. Our research team has already demonstrated the role of silver nitroprusside nanoparticles (SNPNPs) for wound healing and antibacterial activity.

Anti-inflammatory effect of stevioside abates Freund's complete adjuvant (FCA)-induced adjuvant arthritis in rats.

Adjuvant arthritis is a chronic, autoimmune and inflammatory disorder of the joints. The occurrence of disorder causes a severe damage to the connective tissue eventually leading to progressive physical disability and eventual death. The recent years of evidence suggests the anti-inflammatory properties of stevioside, a diterpene glycoside.

Improved delivery of doxorubicin using rationally designed PEGylated platinum nanoparticles for the treatment of melanoma.

Efficient delivery of chemotherapeutic drugs to tumor cells is one of the crucial issues for modern day cancer therapy. In this article, we report the synthesis of poly ethylene glycol (PEG) assisted colloidal platinum nanoparticles (PtNPs) by borohydride reduction method at room temperature. PtNPs are stable at room temperature for more than 2 years and are stable in serum and phosphate buffer (pH = 7.

Arbutin Attenuates Isoproterenol-Induced Cardiac Hypertrophy by Inhibiting TLR-4/NF-κB Pathway in Mice.

Arbutin is a glycoside reported for its anti-oxidant, anti-inflammatory and anti-tumor properties. However, the cardioprotective effect of Arbutin is not well established. The study aims to understand the effect of arbutin on isoproterenol (ISO)-induced cardiac hypertrophy in mice.

Protective effect of galangin against dextran sulfate sodium (DSS)-induced ulcerative colitis in Balb/c mice.

Objective And Design: Inflammatory bowel disease (IBD) is known to cause chronic inflammation in the digestive tract by the immune malfunction. Herein, we demonstrate the protective effect of galangin (GAL), a phytochemical, on LPS-induced inflammation in cultured mouse macrophages (RAW 264.7) and the treatment of DSS-induced ulcerative colitis in Balb/c mice.

Stevioside, a diterpenoid glycoside, shows anti-inflammatory property against Dextran Sulphate Sodium-induced ulcerative colitis in mice.

Inflammatory bowel disease is an umbrella-term used to describe a set of chronic inflammatory conditions that affect the gastro-intestinal tract. Since most of the inflammatory medications in current use have several undesirable side-effects, stevioside, a naturally occurring, high-intensity sweetener was assessed in our study for its anti-inflammatory properties by in-vitro and in-vivo experiments. Stevioside was observed to significantly inhibit the levels of LPS induced elevation of cytokines, TNF-α (P < 0.

β-hCG-induced mutant BRCA1 ignites drug resistance in susceptible breast tissue.

β-hCG expression in breast cancer is highly controversial with reports supporting both protective and tumorigenic effects. It has also been reported that risk of breast cancer at an early age is increased with full-term pregnancies if a woman is a BRCA1 mutation carrier. We have already demonstrated that BRCA1-defective cells express high levels of β-hCG and that when BRCA1 is restored, β-hCG level is reduced.

Delivery of BACE1 siRNA mediated by TARBP-BTP fusion protein reduces β-amyloid deposits in a transgenic mouse model of Alzheimer's disease.

Systemic delivery of nucleic acids to the central nervous system (CNS) is a major challenge for the development of RNA interference-based therapeutics due to lack of stability, target specificity, non-permeability to the blood-brain barrier (BBB), and lack of suitable carriers. Using a designed bi-functional fusion protein TARBP-BTP in a complex with siRNA, we earlier demonstrated knockdown of target genes in the brain of both AβPP-PS1 (Alzheimer's disease, AD) and wild-type C57BL/6 mice. In this report, we further substantiate the approach through an extended use in AβPP-PS1 mice, which upon treatment with seven doses of β-secretase AβPP cleaving Enzyme 1 (BACE1) TARBP-BTP:siRNA, led to target-specific effect in the mouse brain.

Comparative study of toxicological assessment of yttrium oxide nano- and microparticles in Wistar rats after 28 days of repeated oral administration.

Despite their enormous advantages, nanoparticles (NPs) have elicited disquiet over their safety. Among the numerous NPs, yttrium oxide (Y2O3) NPs are utilised in many applications. However, knowledge about their toxicity is limited, and it is imperative to investigate their potential adverse effects.

Novel Cellularly Active Inhibitor Regresses DDAH1 Induced Prostate Tumor Growth by Restraining Tumor Angiogenesis through Targeting DDAH1/ADMA/NOS Pathway.

Dimethylarginine dimethylaminohydrolase1 (DDAH1) inhibitors are important therapeutics by virtue of their ability to control nitric oxide (NO) production by elevating asymmetric dimethylarginine (ADMA) levels. In a screening campaign, we identified that DD1E5 (3-amino-6- tert-butyl-N-(1,3-thiazol-2-yl)-4-(trifluoromethyl)thieno[2,3- b]pyridine-2- carboxamide) inhibits the DDAH1 activity both in vitro and in cultured cells. Mechanistic studies found that DD1E5 is a competitive inhibitor (dissociation constant ( K) of 2.

Supplementation of oat (Avena sativa L.) extract abates alcohol-induced acute liver injury in a mouse model.

Dietary supplementation of oats has been associated with reduced risk of cardiovascular disease, diabetes, and gastrointestinal disorders. The role of oat extract as prophylactic in treating acute liver injury is not thoroughly established. We, therefore, hypothesized that oat extract would exert protective effect against alcohol-induced acute liver injury in a mouse model.

Evaluation of high-fat high-fructose diet treatment in factor VIII (coagulation factor)-deficient mouse model.

Non-alcoholic fatty liver disease (NAFLD)-like conditions enhance the production and action of clotting factors in humans. However, studies examining the effect of NAFLD due to high-fat high-fructose (HFHF) diet in factor VIII-deficient (haemophilia A) animals or patients have not been reported previously. In this study, we investigated the individual role of factor VIII in the progression of diet-induced NAFLD in the factor 8 (F8 ) mouse model system and its consequences on the haemophilic status of the mice.

Ferulic acid protects lipopolysaccharide-induced acute kidney injury by suppressing inflammatory events and upregulating antioxidant defenses in Balb/c mice.

Sepsis-induced acute kidney injury (AKI) is responsible for 70-80% mortality in intensive care patients due to elevated levels of endotoxin, Lipopolysaccharide (LPS) caused by gram-negative infections. Ferulic acid (FA), a phenolic phytochemical is known for its renal protection on various induced models of nephrotoxicity. However, the curative effect of FA in LPS-induced AKI is not well studied.

Metformin regulates mitochondrial biogenesis and senescence through AMPK mediated H3K79 methylation: Relevance in age-associated vascular dysfunction.

Endothelial senescence in conjunction with mitochondrial dysfunction orchestrates age-associated cardiovascular disorders. In this study we investigated the causal link between these two processes and studied the molecular mechanisms by which metformin acts to coordinate the delay of endothelial senescence via enhancing mitochondrial biogenesis/function. AMPK activators metformin and AICAR delayed endothelial senescence via SIRT1-mediated upregulation of DOT1L, leading to increased trimethylation of H3K79 (H3K79me3).