Platelet-Rich Plasma (PRP) Mitigates Kidney Dysfunction in Alloxan-Induced Diabetic Mice via Modulation of Renal Iron Regulatory Genes.

Kidney dysfunction is a prevalent complication of diabetes mellitus, contributing significantly to diabetes-related morbidity and mortality. We aim to explore whether platelet-rich plasma administration can modulate iron regulation mechanism within the kidney, thereby mitigating renal dysfunction associated with diabetes. Albino mice with an average body weight of 20 ± 5 g were randomly divided into five groups (N = 50; n = 10): Control Group, PRP Group, diabetic group (DG), treated group A (TA), and treated group B (TB). A single intraperitoneal dose of alloxan (160 mg/kg of body weight) was administered to mice in the DG and in both treated groups. Upon confirmation of diabetes, the DG was left untreated, while PRP treatment (0.5 ml/kg of body weight) was administered to the TA and TB groups for two and four weeks, respectively. Histological examinations of kidney tissues revealed notable signs of damage in DG, which were subsequently improved upon PRP treatment. Likewise, PRP treatment restored the changes in liver enzymes, oxidative stress biomarkers and serum electrolytes in both treated groups. Furthermore, there was an observed upregulation of iron regulatory genes, such as Renin, Epo, Hepc, Kim1, and Hfe, in the DG, accompanied by a downregulation of Tfr1 and Fpn; however, Dmt1 and Dcytb1 expression remained unaltered. Treatment with PRP restored the expression of iron regulatory genes in both treated groups. This study concluded that PRP treatment effectively restored the renal histochemistry and the expression of renal iron regulatory genes in an alloxan-induced diabetic mice model.

Effect of heterologous platelet-rich plasma on liver and modulation of glucose metabolism and Wnt signalling pathways in diabetic mice.

BACKGROUND: The current study was designed to highlight the effects of heterologous platelet-rich plasma (PRP) on deteriorated hepatic tissues and impaired glucose metabolism of alloxan-induced diabetic mice. METHODS: 30 male mice were divided into a control (CG), PRP (PG), diabetic (DG), and two treated groups (T1G and T2G). PG was given PRP treatment (0.5 ml/kg body weight) twice a week for four weeks. DG, T1G and T2G were given alloxan (150 mg/kg) to induce diabetes. After confirmation, PRP treatment was given to T1G and T2G for two and four weeks respectively while DG was left untreated. Upon completion of the said experimental period, liver samples were taken for histological and gene expression analyses. RESULTS: The study found that the liver tissue of the DG group showed signs of damage, including hepatocyte ballooning, sinusoid dilatation, and collagen deposition. However, these changes were significantly reduced in both T1G and T2G groups. The expression of several genes related to liver function was also affected, with upregulation of Fbp1 and Pklr, and downregulation of Pck1 in the DG group. PRP treatment restored Fbp1 expression and also increased the expression of glycolytic pathway genes Hk1 and Gck, as well as Wnt signalling pathway genes Wnt2, Wnt4, and Wnt9a in both treated groups. CONCLUSION: Current study revealed that heterologous PRP may partly alleviate high glucose levels in diabetics possibly by mediating glucose metabolism via inhibition of Wnt signalling pathway.

A Novel Sprague-Dawley Rat Model Presents Improved NASH/NAFLD Symptoms with PEG Coated Vitexin Liposomes.

Chronic liver disease (CLD) is a global threat to the human population, with manifestations resulting from alcohol-related liver disease (ALD) and non-alcohol fatty liver disease (NAFLD). NAFLD, if not treated, may progress to non-alcoholic steatohepatitis (NASH). Furthermore, inflammation leads to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Vitexin, a natural flavonoid, has been recently reported for inhibiting NAFLD. It is a lipogenesis inhibitor and activates lipolysis and fatty acid oxidation. In addition, owing to its antioxidant properties, it appeared as a hepatoprotective candidate. However, it exhibits low bioavailability and low efficacy due to its hydrophobic nature. A novel rat model for liver cirrhosis was developed by CCL4/Urethane co-administration. Vitexin encapsulated liposomes were synthesized by the 'thin-film hydration' method. Polyethylene glycol (PEG) was coated on liposomes to enhance stability and stealth effect. The diseased rats were then treated with vitexin and PEGylated vitexin liposomes, administered intravenously and orally. Results ascertained the liposomal encapsulation of vitexin and subsequent PEG coating to be a substantial strategy for treating liver cirrhosis through oral drug delivery.

Naringenin (4,5,7-trihydroxyflavanone) suppresses the development of precancerous lesions via controlling hyperproliferation and inflammation in the colon of Wistar rats.

Colon cancer is a world-wide health problem and one of the most dangerous type of cancer, affecting both men and women. Naringenin (4, 5, 7-trihydroxyflavanone) is one of the major flavone glycoside present in citrus fruits. Naringenin has long been used in Chinese's traditional medicine because of its exceptional pharmacological properties and non-toxic nature. In the present study, we investigated the chemopreventive potential of Naringenin against 1,2-dimethyhydrazine (DMH)-induced precancerous lesions, that is, aberrant crypt foci (ACF) and mucin depleted foci (MDF), and its role in regulating the oxidative stress, inflammation and hyperproliferation, in the colon of Wistar rats. Animals were divided into five groups. In groups 3-5, Naringenin was administered at the dose of 50 mg/kg b. wt. orally while in groups 2-4, DMH was administered subcutaneously in the groin at the dose of 20 mg/kg b. wt. once a week for first 5 weeks and animals were euthanized after 10 weeks. Administration of Naringenin ameliorated the development of DMH-induced lipid peroxidation, ROS formation, precancerous lesions (ACF and MDF) and it also reduced the infiltration of mast cells, suppressed the immunostaining of NF-κB-p65, COX-2, i-NOS PCNA and Ki 67 Naringenin treatment significantly attenuated the level of TNF-α and it also prevented the depletion of the mucous layer. Our findings suggest that Naringenin has strong chemopreventive potential against DMH-induced colon carcinogenesis but further studies are warranted to elucidate the precise mechanism of action of Naringenin.

Antifibrotic effects of D-limonene (5(1-methyl-4-[1-methylethenyl]) cyclohexane) in CCl4 induced liver toxicity in Wistar rats.

This study was designed to assess the potential antifibrotic effect of D-Limonene-a component of volatile oils extracted from citrus plants. D-limonene is reported to have numerous therapeutic properties. CCl4 -intduced model of liver fibrosis in Wistar rats is most widely used model to study chemopreventive studies. CCl4 -intoxication significantly increased serum aminotransferases and total cholesterol these effects were prevented by cotreatment with D-Limonene. Also, CCl4 -intoxication caused depletion of glutathione and other antioxidant enzymes while D-Limonene preserved them within normal values. Hydroxyproline and malondialdehyde content was increased markedly by CCl4 treatment while D-Limonene prevented these alterations. Levels of TNF-α, TGF-ß, and α-SMA were also assessed; CCl4 increased the expression of α-SMA, NF-κB and other downstream inflammatory cascade while D-Limonene co-treatment inhibited them. Collectively these findings indicate that D-Limonene possesses potent antifibrotic effect which may be attributed to its antioxidant and anti-inflammatory properties.

Zingerone (4-(4-hydroxy-3-methylphenyl) butan-2-one) protects against alloxan-induced diabetes via alleviation of oxidative stress and inflammation: Probable role of NF-kB activation.

Diabetes is considered as the most common metabolic disease affecting millions of people all around the world. Use of natural herbal medicines can be effective in treating diabetes. Zingerone (4-(4-hydroxy-3-methylphenyl) butan-2-one) a polyphenolic alkanone extracted from ginger has a broad spectrum of pharmacological properties and thus can be used as a promising candidate against various ailments. In the current study we aimed at demonstrating the protective effect of zingerone against diabetes mellitus and elucidating its possible mechanism. Five groups of animals (I-V) were made with ten animals each. Group I (control) was given normal saline orally. Group II (diabetic positive control) was given alloxan at the dose rate of 100 mg/kg bwt once. Group III and IV was given alloxan once at the dose rate of 100 mg/kg bwt. and received oral treatment of zingerone at a dose rate of 50 and 100 mg/kg bwt respectively daily for 21 days. Group V was given alloxan at the dose of 100 mg/kg bwt. and was treated with standard drug glibenclamide at the dose rate of 4.5 mg/kg bwt. daily for 21 days. According to our findings we confirmed that zingerone restrained the alloxan induced oxidative stress by increasing the activity of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and reducing the peroxidative damage. We also confirmed that zingerone suppressed the level of redox sensitive transcription factor NFκB and downregulated other downstream inflammatory cytokines like interleukins (IL1-ß IL-2, IL-6) and tumor necrosis factor alpha (TNF-α). Moreover, the experimental findings suggested that zingerone improved the insulin levels. Taken together our results indicated that zingerone effectively ameliorated the diabetes induced complications which provide a strong theoretical basis for zingerone to be used clinically for treatment of diabetes.

Scientific Appraisal and Therapeutic Properties of Plants Utilized for Veterinary Care in Poonch District of Jammu and Kashmir, India.

The importance of traditional and indigenous knowledge is acknowledged on a worldwide scale for its coexistence principles and sustainable use techniques. In view of this, the present study is an attempt to document the ethno-veterinary plants used by the tribal communities of Western Himalaya. This study also provides the scientific validation of herbal medicines used in ethno-veterinary practices through a reverse pharmacological approach. A total of 59 informants were selected through a non-probability sampling method. Detailed information on the medicinal plants used in ethno-veterinary practices along with their habits and habitats, part/s used, remedy preparation methods, additives/ingredients used during preparation and administration, dosages administered, and route of administration was collected. Data was analyzed for the Relative Frequency of Citations (RFC), Use Values (UV), Informant Consensus Factor (ICF), and Jaccard Index (JI). Further, a reverse pharmacological approach was used for scientific validations of the documented herbal knowledge of plant species. During the study, 56 plant species belonging to 54 genera and 39 families were documented. Asteraceae was the dominant family followed by Lamiaceae, Amaranthaceae and Fabaceae. Life forms were dominated by herbaceous species and leaves were the most common plant parts used. The highest Relative Frequency of Citations (RFC) and Use Values (UV) were recorded for Brassica rapa L. (Brassicaceae). The Pearson correlation coefficient between RFC and UV shows a strong positive correlation between the proportion of uses of a plant species within a sample of informants and the number of times that a particular use of a plant species was mentioned by the informant. Studies of the biological activity of ethno-veterinary plants can provide clues of promising leads for the isolation and identification of useful compounds that may be developed into pharmaceuticals for human welfare.

Psychological impacts of COVID-19 and satisfaction from online classes: disturbance in daily routine and prevalence of depression, stress, and anxiety among students of Pakistan.

The present study investigated the (i) socio-demographic predictors of psychological distress, (ii) socio-demographic predictors of satisfaction from online classes, and (iii) the relationship between psychological distress and satisfaction from online classes among university students of Pakistan during the COVID-19 pandemic. An online questionnaire-based survey was conducted. A total of 2220 respondents that was enrolled at the University of the Punjab (PU), University of Management and Technology (UMT), and the University of Central Punjab (UCP) were involved in the current study. Data were collected at a 64% response rate and analyzed with SPSS IBM Version 21.0. Results revealed that approximately 41% of the students were facing severe psychological distress while about 65% were found unsatisfied with online classes. Besides, a linear negative relationship between the independent variable, i.e. psychological distress and the dependent variable, i.e. satisfaction from online classes was found. Therefore, to minimize the level of psychological distress and increase students' satisfaction with online classes it is highly recommended to take precautionary measures by the relevant stakeholders.

Rational Design and Synthesis of Naphthalene Diimide Linked Bis-Naphthalimides as DNA Interactive Agents.

A molecular modeling assisted rational design and synthesis of naphthalene diimide linked bis-naphthalimides as potential DNA interactive agents is described. Chemical templates incorporating naphthalene diimide as a linker in bis-naphthalimide motif were subjected to molecular docking analysis at specific intercalation and telomeric DNA G-quadruplex sites. Excellent results were obtained, which were better than the standards. A short and convenient synthetic route was employed to access these hybrids experimentally, followed by evaluation of their ability to cause thermal denaturation of DNA and cytotoxic properties along with ADME predictions. The obtained results provided useful insights and two potential molecules were identified for further development.

Preclinical Evidence for the Pharmacological Actions of Glycyrrhizic Acid: A Comprehensive Review.

Glycyrrhiza glabra L. (Family: Fabaceae) is one of the important traditional medicinal plant used extensively in folk medicine. It is known for its ethnopharmacological value in curing a wide variety of ailments. Glycyrrhizin, an active compound of G. glabra, possesses anti-inflammatory activity due to which it is mostly used in traditional herbal medicine for the treatment and management of chronic diseases. The present review is focused extensively on the pharmacology, pharmacokinetics, toxicology, and potential effects of Glycyrrhizic Acid (GA). A thorough literature survey was conducted to identify various studies that reported on the GA on PubMed, Science Direct and Google Scholar.

Effects of palm oil on structural and in vitro digestion properties of cooked rice starches.

The glycemic potency of rice depends upon the rate and extent of starch hydrolysis by pancreatic amylase and intestinal alpha-glucosidases. However, complexation of starch molecules with lipids is known to reduce the enzymic hydrolysis. In this study, we elucidated the varietal effect of rice starches on the formation of amylose-lipid complex, after cooking with palm oil, a common cooking oil. The amount of complexed lipid followed the order of black (2.5%), brown (2.5%), white (1.5%) and waxy (0.5%) rice starches. After heating with palm oil, the relative crystallinity of all the rice starches were destroyed whilst a V-type peak at 20° 2θ was increased, indicating the formation of amylose-lipid complex. This is also suggested from the DSC data where the melting enthalpy increased significantly after cooking in palm oil for all rice samples. The formation of amylose-lipid complex reduced the in vitro starch digestibility, enhancing the resistance starch content whilst decreasing the rapid and slow digestion fractions of non-waxy varieties. The rate and extent of in vitro starch hydrolysis seems to be dependent on the presence or absence of amylose fraction. With the mechanistic details, the present study suggests the applicability of palm oil addition during the rice cooking to enhance its nutritional functionality.

Particle size affects structural and in vitro digestion properties of cooked rice flours.

The aim of this study was to identify the contributions made by size fractions of four milled rice (i.e., waxy, white, black and brown rice) to structural and in vitro starch digestion properties after cooking. Rice grains were hammer-milled in a controlled manner, and the coarse (300-450 µm), medium (150-300 µm) and fine size (<150 µm) fractions were segregated through vertical sieving. All samples displayed monophasic digestograms, and starch digestion rate and extent for size fractionated rice flours were predicted through the Logarithm of Slope model. It was found that digestion rate and extent were markedly reduced with increasing particle size within each rice variety. Of the four rice varieties, non-waxy rice flour fractions showed lower digestion rate and extent compared to the waxy counterpart, possibly due to the formation starch-lipid complexes as judged by XRD with ca. 4%-8% V-type crystalline structure remained after cooking. We suggested that the less rigid morphological structure and almost amorphous conformation lead to the high digestion rate and extent during simulated intestinal starch digestion. These findings will help develop functional rice ingredients with desirable digestion behaviour and attenuated postprandial glycemic responses.

Bioengineered silver nanoparticles using Curvularia pallescens and its fungicidal activity against Cladosporium fulvum.

Microorganisms based biosynthesis of nanomaterials has triggered significant attention, due to their great potential as vast source of the production of biocompatible nanoparticles (NPs). Such biosynthesized functional nanomaterials can be used for various biomedical applications. The present study investigates the green synthesis of silver nanoparticles (Ag NPs) using the fungus Curvularia pallescens (C. pallescens) which is isolated from cereals. The C. pallescens cell filtrate was used for the reduction of AgNO3 to Ag NPs. To the best of our knowledge C. pallescens is utilized first time for the preparation of Ag NPs. Several alkaloids and proteins present in the phytopathogenic fungus C. pallescens were mainly responsible for the formation of highly crystalline Ag NPs. The as-synthesized Ag NPs were characterized by using UV-Visible spectroscopy, X-ray diffraction and transmission electron microscopy (TEM). The TEM micrographs have revealed that spherical shaped Ag NPs with polydisperse in size were obtained. These results have clearly suggested that the biomolecules secreted by C. pallescens are mainly responsible for the formation and stabilization of nanoparticles. Furthermore, the antifungal activity of the as-prepared Ag NPs was tested against Cladosporium fulvum, which is the major cause of a serious plant disease, known as tomato leaf mold. The synthesized Ag NPs displayed excellent fungicidal activity against the tested fungal pathogen. The extreme zone of reduction occurred at 50 µL, whereas, an increase in the reduction activity is observed with increasing the concentration of Ag NPs. These encouraging results can be further exploited by employing the as synthesized Ag NPs against various pathogenic fungi in order to ascertain their spectrum of fungicidal activity.

Evaluation of iron deficiency anaemia for gastrointestinal causes in patients without GI symptoms in high prevalent GI malignancy zones.

BACKGROUND AND STUDY AIMS: Gastric cancer is highly prevalent in Kashmir, as are lower gastrointestinal (LGI) malignancies. Colonic cancer, gastric cancer, and coeliac disease are the most important gastrointestinal (GI) causes of iron deficiency anaemia (IDA) worldwide. Approximately 9% of patients with IDA present with a suspicious lesion in the GI tract upon examination. However, the absence of GI symptoms and a possible lesion accounting for blood loss in IDA have not been studied in this zone with a high prevalence of GI malignancy. We aimed to examine IDA patients without GI symptoms to determine the most plausible cause of their blood loss. PATIENTS AND METHODS: A total of 100 patients with IDA and 250 control subjects without IDA and referred for gastrointestinal endoscopy were enrolled in a cross-sectional, comparative study. Patients presenting with a significant lesion proportionate to their anaemia in the upper GI tract were not examined further, if no further strong indications were present. RESULTS: Twenty-nine patients (29%) were found to have malignancy: 13 with gastric cancer and 16 with colonic malignancies. Other apparent causes of GI blood loss included peptic ulcer disease in 10 (10%) patients, haemorrhoids in 22 (25%), polyps in eight (three in the upper GI tract and five in the LGI tract), gastric erosions in eight (8%), and angiodysplasia, diverticulitis, and trichuriasis in two (2%) each. CONCLUSION: In light of the high incidence of GI malignancies in this patient group, a low threshold for GI screening as well as mass screening for IDA is needed.