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Cardiovascular diseases (CVD) cause significant global morbidity, mortality and public health burden annually. CVD alters richness, diversity, and composition of Gut microbiota along with RAS and histopathological differences. Present study explores Metformin role in mitigating doxorubicin induced cardiovascular toxicity/remodeling. Animals were divided into 4 groups with n=6: Group I (N. Control) free access to diet and water; Group II (MET. Control) on oral Metformin (250 mg/kg) daily; Group III (DOX. Control) alternate day intraperitoneal Doxorubicin (3 mg/kg) totaling 18 mg/kg; Group IV (DOX. MET. Control) received both daily oral Metformin (250 mg/kg) and alternate day Doxorubicin (3 mg/kg). Gut microbial analysis was made from stool before animals were sacrificed for biochemical and histopathological analysis. Significant alterations were observed in ɑ and β-diversity with new genus from Firmicutes, specifically Clostridia_UCG-014, Eubacterium ruminantium, and Tunicibacter, were prevalent in both the DOX. Control and DOX.MET groups. Proteobacteria, represented by Succinivibrio, were absent in all groups. Additionally, Parabacteroides from the Bacteroidia phylum was absent in all groups except the N. control. In the DOX.MET Control group, levels of Angiotensin II ( 7.75± 0.49 nmol/min, p

Cardiac dysfunction can be prevented by addressing risk factors including unhealthy diet with other lifestyle modifications. The present study demonstrates the effect of diet mixed with sea and table salts on cardiac remodeling with respect to CKMB, renin, angiotensin II, interleukin-6 and 10. Animals divided into six groups. Normal control, Table salt (0.3%), Natural sea salt (0.3%), Doxorubicin-induced cardiac remodeling control (2 mg/kg), + Normal table salt (0.3%) and Doxorubicin + Natural sea salt (0.3%) . Serum analysis and histopathology of heart, liver and kidney was performed. Significant variation (P

Breast cancer (BC) is one of the most common cancers in women and is a major cause of female cancer-related deaths. BC is a multifactorial disease caused by the dysregulation of many genes, raising the need to find novel drugs that function by targeting several signaling pathways. The antitumoral drug thymoquinone (TQ), found in black seed oil, has multitargeting properties against several signaling pathways. This study evaluated the inhibitory effects of TQ on the MCF7 and T47D human breast cancer cell lines and its antitumor activity against BC induced by a single oral dose (65 mg/kg) of 7,12-dimethylbenzanthracene (DMBA) in female rats. The therapeutic activity was evaluated in DMBA-treated rats who received oral TQ (50 mg/kg) three times weekly. TQ-treated MCF7 and T47D cells showed concentration-dependent inhibition of cell proliferation and induction of apoptosis. TQ also decreased the expression of DNA methyltransferase 1 (DNMT1) in both cancer cell types. In DMBA-treated animals, TQ inhibited the number of liver and kidney metastases. These effects were associated with a reduction in DNMT1 mRNA expression. These results indicate that TQ has protective effects against breast carcinogens through epigenetic mechanisms involving DNMT1 inhibition.

Abstract A comprehensive understanding of the quality of life (QoL) is essential to establish long-term survivor care plans. The present study was aimed at the assessment of QoL of BC survivors with special emphasis on post-treatment physical, emotional, social, and spiritual challenges. We have assessed the QoL of 250 female BC survivors of all age groups through demographic factors. Volunteer BC survivors were registered in the present study who had got treatment from the Institute of Nuclear Medicine and Oncology (INMOL) hospital and Mayo hospital Lahore. An informed consent form was signed by each participant. The physical, psychological, and spiritual well-being was evaluated by a questionnaire filled with the help of respondents. The average age of BC survivors was 52 ± 7.8 years. Most of them (83%) complained of fatigue during daily life activities, 75.1% body pain or headache, 77.1% had problems with appetite, 63.2% reported weight loss, 77.1% had sleep problems, and 90.5% were feeling general weakness. Only 16.2% were satisfied with their physical health and 2% were not satisfied with their medication. Psychologically, 74.4% were feeling different levels of anxiety, only 10% of them were hoping to achieve a desired life. Age group 21 to 40 years reported better physical health, those with 40–50 years of age and family history of BC have shown better mental strength. The physical and psychological health of survivors from rural areas was comparatively better than those from urban areas. The BC survivor women have to face several physical, psychological and social challenges. The majorities of them complain of anxiety, body pain, fatigue, sleep problems, general weakness, and fear about the future. Our findings suggest the need for psychological support, physical activity a comprehensive post-diagnosis and post-treatment physical and mental health assistance plan for all BC survivors. Implications for Cancer Survivors. Survivors of breast cancer experience various challenges including anxiety, sleep problems, body pain, fatigue, and fear about the future. The psychological, physical and social factors make a great difference in their quality of life.

Objective: Researchers have confirmed that chronic administration of drugs at high doses causes genotoxicity which serve as first step in development of cancers. Apremilast, a phosphodiesterase-4 inhibitor is Food and Drug Administration (FDA) approved drug for Psoriatic Arthritis. The present study designed to conduct genotoxicity testing using the genotoxic study which give simple, sensitive, economical and fast tools for the assessment of damage of genetic material. Methods: To conduct genotoxicity study of Apremilast, 60 Swiss albino male mice divided into 6 groups (n = 10). Group1 served as a normal control group without any treatment, Group 2 treated as a disease control and administered with cyclophosphamide 40 mg/kg, IP. Group 3, 4, 5 and 6 treated as test groups and received 10, 20, 40 and 80 mg/kg/day Apremilast respectively. The total duration of study was 13 weeks. At termination day animals were sacrificed and chromosomal aberration assay (BMCAA) and micronucleus assay (BMMNA) were performed to know the genotoxicity potential of Apremilast. Results: The results indicates significant rise in chromosomal aberrations (CA) frequency in bone marrow cells and decrease in the MI of the disease control animals as well as Apremilast treated groups. Further significant (p

Diazepam is a medicine of the family benzodiazepine, used to treat various CNS disorders. To date, no study is available for biochemical analysis of diazepam in cardiac dysfunction. This study aimed to determine the effect of diazepam in stress-induced cardiac dysfunctions in rats. Male Wistar Albino rats were divided into four groups with six animals in each group for 90 days of the experimental protocol. Group1 served as a Normal Control (NC), Groups 2, as a Disease Control (DC), Group 3 as a Diazepam Control (DIC), and Group 4 as a Disease + Diazepam Treatment (DDT). Disease Control and Disease + Diazepam Treatment animals exposed to regular stress by forced swimming exercise method for 3 months. Diazepam Control and Disease + Diazepam Treatment received 5 mg/kg/p.o the daily dose of diazepam. At the end of the protocol, animals were sacrificed, heart preserved, blood collected, and utilized for biochemical estimations. Heart weight was increased in DC as compared to NC. Serum levels of cardiac biomarkers, creatine phosphokinase (CPK), creatine kinase-MB (CPK-MB), lactate dehydrogenase (LDH), High sensitivity C-reactive protein (hs-CRP) and troponin I (TnI) were significantly increased in DC as compared to NC. Heart tissue examined for histological changes. The altered serum levels of CPK, CPK-MB, LDH, hs-CRP, and TnI were significantly restored by the treatment of diazepam. Serum levels of Sodium, Potassium, Calcium, and Magnesium was increased in DC animals as compared to NC. The altered ionic level was also restored by the treatment of diazepam. Level of various cardiac markers and ions in the plasma were also slightly elevated in DIC. Histopathological studies are also in agreement with serological examinations and bonafide cardioprotective influences of diazepam in cardiac dysfunction. Conclusively research findings endorse the cardioprotective effect of diazepam in stress-induced cardiac dysfunction in rats.

Nigella sativa L. seed commonly known as black seed, extensively used as a folk medicine in Middle East and Asian subcontinent. Traditionally it is used as an adjunct therapy along with modern medicine to counter the adverse effects. Pure thymoquinone or isolated compounds are not free from adverse effects. The present study was undertaken to evaluate N. sativa seeds powder impact on the fluconazole (FLZ) induced toxicities in the liver and kidneys. Male Wistar rats were acclimatized, divided into four groups each group with six animals. Experimental animals were subjected to an FLZ dose of 50 mg per kg of body mass. The toxic effects of FLZ treatment were manifested and animals were given 1000 mg of N. sativa seeds powder per kg of body weight to observe any retrieval. Dissected animals were evaluated for biochemical and histopathology alterations. Based on findings, it can be concluded that N. sativa seeds powder restored various altered biochemical parameters induced by fluconazole and can be used along with fluconazole in the treatment of fungal infections.

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This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12906-016-1470-9.

This work evaluates nano-lipid carrier of ganoderic acid (GA) and molecular docking on various cancer signaling pathways, an attempt to improve the hepatic condition associated with hepatic carcinoma (HCC) induced by diethyl-nitrosamine (DEN) in Wistar rats. Molecular docking mechanism of GA was performed through binding simulation analysis for various cancer signaling pathway, viz., Bcl-2, Pl3K, NF-κB, Akt/PKB, and Stat-3. Double emulsion solvent displacement method was implied for preparation of GA-loaded nano-lipid carrier. GA-NLCs were evaluated for drug loading capacity, entrapment efficiency, particle size, gastric stability, in vitro drug release, cytotoxicity, cellular uptake, and in vivo studies including macroscopical, hepatic injury markers, non-hepatic, biochemical, antioxidant parameters, and histopathological evaluation. HCC was induced by intraperitoneal injection of DEN (200 mg/kg). Both in vivo and molecular docking results were compatible in establishing the alteration in hepatic nodules, hepatic, non-hepatic, and antioxidant parameters, in a significant manner (p

Microtubule affinity regulating kinase 4 (MARK4) regulates the mechanism of microtubules by its ability to phosphorylate the microtubule-associated proteins (MAP’s). MARK4 is known for its major role in tau phosphorylation via phosphorylating Ser262 residue in the KXGS motif, which results in the detachment of tau from microtubule. In lieu of this vital role in tau pathology, a hallmark of Alzheimer’s disease (AD), MARK4 is a druggable target to treat AD and other neurodegenerative disorders (NDs). There is growing evidence that NDs and diabetes are connected with many pieces of literature demonstrating a high risk of developing AD in diabetic patients. Metformin (Mtf) has been a drug in use against type 2 diabetes mellitus (T2DM) for a long time; however, recent studies have established its therapeutic effect in neurodegenerative diseases (NDs), namely AD, Parkinson’s disease (PD) and amnestic mild cognitive impairment. In this study, we have explored the MARK4 inhibitory potential of Mtf, employing in silico and in vitro approaches. Molecular docking demonstrated that Mtf binds to MARK4 with a significant affinity of −6.9 kcal/mol forming interactions with binding pocket’s critical residues. Additionally, molecular dynamics (MD) simulation provided an atomistic insight into the binding of Mtf with MARK4. ATPase assay of MARK4 in the presence of Mtf shows that it inhibits MARK4 with an IC50 = 7.05 µM. The results of the fluorescence binding assay demonstrated significant binding of MARK4 with a binding constant of 0.6 × 106 M−1. The present study provides an additional axis towards the utilization of Mtf as MARK4 inhibitor targeting diabetes with NDs.

The objective of this study was to evaluate the anticancer effects of Melstoma malabathricum L. (MM) MDA-MB-231 human breast cancer and in vivo mammary tumor model and decipher the potential mechanism. The phyto-constituents in the extract have been identified by liquid chromatography-mass spectrometry (LC–MS). The anti-cancer activity of MM extract was tested on MDA-MB-231 human breast cancer cells. Chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) was used for the induction of breast cancer in rodents. Burden, volume, tumor incidence, pro-inflammatory cytokines, antioxidant parameters and mitochondrial parameters were estimated. Histological analysis was determined in mammary gland, vagina, uterus, heart, liver, lung and renal tissues. LC–MS showed the 21 phyto-constituents present in the extract of MM. MM extract showed the potent cytotoxicity against MDA-MB-231 cells and exhibited the IC50 value (14.6 μM). MM extract significantly decreased the body weight and altered the organ weight such as ovary, uterus, liver, spleen, lungs, renal, adrenal and brain tissue. MM extract significantly down-regulated the tumor incidence, tumor burden and average tumor weight at dose dependently manner. MM extract significantly altered the antioxidants activity in term of augmented the level of superoxide dismutase (SOD), catalase (CAT) and suppressed the level of malonaldehyde (MDA); pro-inflammatory cytokines levels such as reduced the level of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) in the serum, hepatic and mammary gland tissue in DMBA induced mammary gland tumor rats. MM extract significantly (P

Cardiac disorders contribute to one of the major causes of fatality across the world. Hypertensive patients, even well maintained on drugs, possess a high risk to cardiovascular diseases. It is, therefore, highly important to identify different factors and pathways that lead to risk and progression of cardiovascular disorders. Several animals and human studies suggest that taxonomical alterations in the gut are involved in the cardiovascular physiology. In this article, with the help of various experimental evidences, we suggest that the host gut-microbiota plays an important in this pathway. Short chain fatty acids (SCFAs) and Trimethyl Amine -n-Oxide (TMAO) are the two major products of gut microbiome. SCFAs present a crucial role in regulating the blood pressure, while TMAO is involved in pathogenesis of atherosclerosis and other coronary artery diseases, including hypertension. We prove that there exists a triangular bridge connecting the gap between dietary salt, hypertension and gut microbiome. We also present some of the dietary interventions which can regulate and control microbiota that can prevent cardiovascular complications.We strongly believe that this article would improve the understanding the role of gut microbiota in hypertension, and will be helpful in the development of novel therapeutic strategies for prevention of hypertension through restoring gut microbiome homeostasis in the near future

Objectives: Breast cancer is one of the most commonly diagnosed cancer among women globally. Shogaol, the active constituent of many spices belonging to the Zingiberaceae family, has received wide attention among other shogaols in terms of its anticancer activity against different neoplasms. To date, its efficacy at the detailed molecular level against breast cancer has not been established. Methods: In the current study, we investigated the cytotoxic potential and the underlying molecular details of 6-shogaol against breast adenocarcinomacells (MCF-7), and breast ductal carcinoma cells (T47D). Cytotoxicity assay, cell cycle analysis. Real-time PCR (qPCR), apoptosis and autophagy techniques were used for the determination and molecular investigation of its anticancer properties. Results: The current study shows that, Notch signaling downregulation (Hes1 and CyclinD1 genes), caused by 6-shogaol, lead to antiproliferative activity in breast cancer cells. The study further shows that treatment with 6-shogaol induced significant and time dependent cell cycle accumulation in G2/M-phase. 6-Shogaol also induced significant apoptosis in breast cancer cells. Interestingly, 6-shogaol inhibited autophagy in breast cancer cell lines, which might force these cells to undergo apoptosis. Conclusion: 6-Shogaol is a promising candidate to be considered as a treatment of breast cancer.

Phytophthora infestans (mont) de Bary is a pathogen of great concern across the globe, and accurate detection is an important component in responding to the outbreaks of potential disease. Although the molecular diagnostic protocol used in regulatory programs has been evaluated but till date methods implying direct comparison has rarely used. In this study, a known area soil samples from potato fields where light blight appear every year (both A1 and A2 mating type) was assayed by soil bait method, PCR assay detection and quantification of the inoculums. Suspected disease symptoms appeared on bait tubers were further confirmed by rapid PCR, inoculums were quantified through Real Time PCR, which confirms presence of P. infestans. These diagnostic methods can be highly correlated with one another. Potato tuber baiting increased the sensitivity of the assay compared with direct extraction of DNA from tuber and soil samples. Our study determines diagnostic sensitivity and specificity of the assays to determine the performance of each method. Overall, molecular techniques based on different types of PCR amplification and Real-time PCR can lead to high throughput, faster and more accurate detection method which can be used in quarantine programmes in potato industry and diagnostic laboratory.

Allicin (diallylthiosulfinate) is a defense molecule produced by cellular contents of garlic (Allium sativum L.). On tissue damage, the non-proteinogenic amino acid alliin (S-allylcysteine sulfoxide) is converted to allicin in an enzyme-mediated process catalysed by alliinase. Allicin is hydrophobic in nature, can efficiently cross the cellular membranes and behaves as a reactive sulfur species (RSS) inside the cells. It is physiologically active molecule with the ability to oxidise the thiol groups of glutathione and between cysteine residues in proteins. Allicin has shown anticancer, antimicrobial, antioxidant properties and also serves as an efficient therapeutic agent against cardiovascular diseases. In this context, the present review describes allicin as an antioxidant, and neuroprotective molecule that can ameliorate the cognitive abilities in case of neurodegenerative and neuropsychological disorders. As an antioxidant, allicin fights the reactive oxygen species (ROS) by downregulation of NOX (NADPH oxidizing) enzymes, it can directly interact to reduce the cellular levels of different types of ROS produced by a variety of peroxidases. Most of the neuroprotective actions of allicin are mediated via redox-dependent pathways. Allicin inhibits neuroinflammation by suppressing the ROS production, inhibition of TLR4/MyD88/NF-κB, P38 and JNK pathways. As an inhibitor of cholinesterase and (AChE) and butyrylcholinesterase (BuChE) it can be applied to manage the Alzheimer’s disease, helps to maintain the balance of neurotransmitters in case of autism spectrum disorder (ASD) and attention deficit hyperactive syndrome (ADHD). In case of acute traumatic spinal cord injury (SCI) allicin protects neuron damage by regulating inflammation, apoptosis and promoting the expression levels of Nrf2 (nuclear factor erythroid 2-related factor 2). Metal induced neurodegeneration can also be attenuated and cognitive abilities of patients suffering from neurological diseases can be ameliorates by allicin administration.

A new marker for rapid and early identification and detection of Phytophthora infestans, the causal agent of late blight of potato and tomato has been developed using PCR. Amplification products obtained from random amplified monomorphic DNA (RAPD) reactions were cloned and sequenced, and two extended primer sets (PITH2-F/PITH2-R) were designed from the resulting data that were used to detect sequenced-characterized DNA markers. A single 1.5 kb DNA amplification product was consistently obtained from primer OPA 12 that was specific for P. infestans but was not produced from other Phytophthora species and fungal pathogen of potato. A 524 bp amplification product was also produced from naturally infected tubers known to be infected with the fungus as verified by microscopic examination. A similar PCR product was obtained from sterile soil samples artificially infested with P. infestans inoculums. This primer is a highly specific to P. infestans only. This PCR based assay enables detection of P. infestans from host tissues, sporangia and Oospores present in the soil in a single day.

Garcinia mangostana L. (Fruit) has been commonly used as folklore drug in the treatment of various types of diseases. The present experiment was designed to evaluate the potential effect of α-mangostin mediated pharmacological modulation of hepatic carbohydrate metabolism in streptozotocin (STZ) induced diabetic rats. Oral glucose tolerance test (OGTT) was performed in normoglycemic rats. Single intraperitoneal injection of STZ (60 mg/kg, body weight) was used for induction the diabetes in Swiss albino (Wistar strain) rats. The rats were divided into different groups. Blood glucose level, body weight, insulin, glycated hemoglobin and hemoglobin levels were recorded at regular intervals. Biochemical parameters, liver enzymes, lipid profile, antioxidant parameters and inflammatory cytokine mediators were also scrutinized. Histopathology study of kidney, pancreas and liver were performed. The result of OGTT study depicted the better utilization of glucose in experimental rats. STZ induced diabetic rats treated with α-mangostin (25, 50 and 100 mg/kg, p.o.) and glibenclamide depicted the decline in the level of blood glucose; enhanced body weight and showed the better utilization of glucose by different organs. STZ induced diabetic rats treated with α-mangostin illustrated the increased level of plasma insulin, hemoglobin, hexokinase, HDL, total protein, SOD, CAT, GSH and declined level of glycated hemoglobin, fructose-1-6-biphosphatase, glucose-6-Phosphatase, TC, TG, LDL, VLDL, CRE, BUN, SGOT, SGPT, ALP and LPO at effective dose dependent manners. Histological study showed the inflamed blood vessels in diabetic kidney, which was less in α-mangostin treated rats; diabetic pancreatic showed the complete damage of β cells, islets, aciini and producing necrosis, but all damage was less obvious in α-mangostin treating group rats; diabetic liver showed the damage of hepatocytes as well as central vein but was less in treated groups. Considering the above results, α-mangostin shows potential to develop a medicine for diabetes, hyperlipidemia, renal and hepatic protection as combinational or mono-therapy.

A correct detection and appropriate identification of causal pathogens associated with crop plants or seeds are considered to be the most important issue in designing the proper management plans for plant diseases. This study was designed to detect Phytophthora infestans inoculum from potato grown soil. A high detection rate of P.infestans was obtained from the naturally infested soil of potato fields. Naturally soils were firstly moistened in a plastic pots and then pre-incubated at ±18°C for 3 days, baiting with potato tuber slice for 24, 48, and 72 h. The baits were then thoroughly washed, flooded with 10–15 ml of distilled water in Petri-dishes and incubated under continuous darkness in chamber ±18ºC. Sporangia started to emerge from the margins of potato tuber slice. They were easily observed under the stereomicroscope. Pure culture of the fungus was obtained by isolating from baited tubers on a Rye Agar medium. This is the first report of recovery of P. infestans from naturally infested potato growing soils using susceptible potato tuber (K. Bahar) as bait in India. All isolates were determined to be A2 mating type.

Nowadays, use of alternative and complementary therapies with mainstream medicine has gained the momentum. Aromatherapy is one of the complementary therapies which use essential oils as the major therapeutic agents to treat several diseases. The essential or volatile oils are extracted from the flowers, barks, stem, leaves, roots, fruits and other parts of the plant by various methods. It came into existence after the scientists deciphered the antiseptic and skin permeability properties of essential oils. Inhalation, local application and baths are the major methods used in aromatherapy that utilize these oils to penetrate the human skin surface with marked aura. Once the oils are in the system, they remodulate themselves and work in a friendly manner at the site of malfunction or at the affected area. This type of therapy utilizes various permutation and combinations to get relief from numerous ailments like depression, indigestion, headache, insomnia, muscular pain, respiratory problems, skin ailments, swollen joints, urine associated complications etc. The essential oils are found to be more beneficial when other aspects of life and diet are given due consideration. This review explores the information available in the literature regarding therapeutic, medical, cosmetic, psychological, olfactory, massage aromatherapy, safety issues and different plants used in aromatherapy. All the available information was compiled from electronic databases such as Academic Journals, Ethnobotany, Google Scholar, PubMed, Science Direct, Web of Science, and library search.

Introduction: Rabeprazole, a member of substituted benzimidazoles, inhibits the final step in gastric acid secretions. This drug claims to cause fastest acid separation (due to higher pKa), and more rapidly converts to the active species to aid gastric mucin synthesis. The most significant pharmacological action of Rabeprazole is dose dependent suppression of gastric acid secretion; without anticholinergic or H2-blocking action. It completely abolishes the hydrochloric acid secretion as it is powerful inhibitor of gastric acid. Rabeprazole is acid labile and hence commonly formulated as an enteric coated tablet. The absorption of rabeprazole occurs rapidly as soon as tablet leaves the stomach. Aim: In the present study an attempt was made to formulate and evaluate Rabeprazole sustained release matrix tablet using wet granulation technique incorporating various polymers like HPMC-E15, Carbopol934, and sodium carboxymethyl cellulose (CMC). Materials and Methods: The Formulated tablets were evaluated for different physicochemical properties like rheological properties, weight variation, thickness, hardness, % friability, in vitro release studies and drug content. Results: Studies revealed that all the physicochemical parameters comply with the official standards. The in vitro release studies exhibits the release up to 90%, over a prolonged period of time which confirms the extended release profile of formulation, having better bioavailability as well as decreased dosing frequency with reduced doses. Conclusion: The sustained release matrix tablets of rabiprazole shown better bioavailability, efficacy and potency, when compared with official standards.

Withdrawn by the Editor