Interaction of coumarin triazole analogs to serum albumins: Spectroscopic analysis and molecular docking studies.

The interaction of triazole substituted 4-methyl-7-hydroxycoumarin derivatives (CUM1-4) with serum albumin (bovine serum albumin [BSA] and human serum albumin [HSA]) have been studied employing ultraviolet-visible (UV-Vis), fluorescence, circular dichroism (CD) spectroscopy, and molecular docking methods at physiological pH 7.4. The fluorescence quenching occurred with increasing concentration of CUMs, and the binding constant of CUM derivatives with BSA and HSA obtained from fluorescence quenching experiment was found to be ~ 104 L mol-1 . CD study showed conformational changes in the secondary structure of serum albumin upon titration of CUMs. The observed experimental results were further validated by theoretical studies involving density functional theory (DFT) and molecular docking.

Organosulfur Compounds in Aged Garlic Extract Ameliorate Glucose Induced Diabetic Cardiomyopathy by Attenuating Oxidative Stress, Cardiac Fibrosis, and Cardiac Apoptosis.

BACKGROUND: Diabetic cardiomyopathy has emerged as a major cause of cardiac fibrosis, hypertrophy, diastolic dysfunction, and heart failure due to uncontrolled glucose metabolism in patients with diabetes mellitus. However, there is still no consensus on the optimal treatment to prevent or treat the cardiac burden associated with diabetes, which urges the development of dual antidiabetic and cardioprotective cardiac therapy based on natural products. This study investigates the cardiotoxic profile of glucose and the efficacy of AGE against glucose-induced cardiotoxicity in H9c2 cardiomyocytes. MATERIAL METHODS: The cellular metabolic activity of H9c2 cardiomyocytes under increasing glucose concentration and the therapeutic efficacy of AGE were investigated using the MTT cell cytotoxicity assay. The in vitro model was established in six groups known as 1. control, 2. cells treated with 25 µM glucose, 3. 100 µM glucose, 4. 25 µM glucose +35 µM AGE, 5. 100 µM glucose + 35 µM AGE, and 6. 35 µM AGE. Morphological and nuclear analyses were performed using Giemsa, HE, DAPI, and PI, respectively, whereas cell death was simultaneously assessed using the trypan blue assay. The antioxidant potential of AGE was evaluated by DCFH-DA assay, NO, and H202 scavenging assay. The activities of the antioxidant enzymes catalase and superoxide dismutase were also investigated. The antiglycative potential of AGE was examined by antiglycation assays, amylase zymography, and SDS PAGE. These results were then validated by in silico molecular docking and qRTPCR. RESULTS: Hyperglycemia significantly reduced cellular metabolic activity of H9c2 cardiomyocytes, and AGE was found to preserve cell viability approximately 2-fold by attenuating oxidative, fibrosis, and apoptotic signaling molecules. In silico and qRTPCR studies confirmed that organosulfur compounds target TNF-α, MAPK, TGF-ß, MMP-7, and caspase-9 signaling molecules to ameliorate glucose-induced cardiotoxicity. CONCLUSION: AGE was found to be an antidiabetic and cardioprotective natural product with exceptional therapeutic potential for use as a novel herb-drug therapy in the treatment of diabetic cardiomyopathy in future therapies.

Therapeutic Potential of Stable Organosulfur Compounds of Aged Garlic.

Aged garlic extract (AGE) is an odorless derivative of garlic prepared by extracting garlic cloves in an aqueous solution for twenty months. During the process of aging, reactive organosulfur compounds such as allicin present in garlic are converted to their stable isoforms such as S- Allyl cysteine. The unstable organo sulfurs in garlic (Allium sativum L.) have been reported to cause problems in the gastrointestinal (GI) tract with an extremely pungent odor to attain its therapeutic potential. But these pharmacologically safer sulfur compounds of AGE have been studied and reported to have exceptional therapeutic potential in human health and various diseases. SAllyl cysteine (SAC), Diallyl disulfide (DADS), Diallyl trisulfide (DATS), S-allyl-mercaptocysteine (SAMC), are the most studied organosulfur compounds in in-vitro as well as in-vivo research. Biomedical research suggests that these phytoconstituents exhibit antioxidant, cardioprotective, cancer preventive, neuroprotective, immunomodulatory, antilipidemic, antidiabetic, hepatoprotective, and antiobesity effects. The therapeutic potential of aged garlic extract has been found to be extensively beneficial in these conditions, and provide a vast future in biomedical chemistry, herbdrug synergy and drug designing. The purpose of this review is to provide a mechanistic understanding of various organosulfur compounds of AGE in human health and disease based on data provided in the literature.

Ferrous and ferric complexes with cyclometalating N-heterocyclic carbene ligands: a case of dual emission revisited.

Iron N-heterocyclic carbene (FeNHC) complexes with long-lived charge transfer states are emerging as a promising class of photoactive materials. We have synthesized [FeII(ImP)2] (ImP = bis(2,6-bis(3-methylimidazol-2-ylidene-1-yl)phenylene)) that combines carbene ligands with cyclometalation for additionally improved ligand field strength. The 9 ps lifetime of its 3MLCT (metal-to-ligand charge transfer) state however reveals no benefit from cyclometalation compared to Fe(ii) complexes with NHC/pyridine or pure NHC ligand sets. In acetonitrile solution, the Fe(ii) complex forms a photoproduct that features emission characteristics (450 nm, 5.1 ns) that were previously attributed to a higher (2MLCT) state of its Fe(iii) analogue [FeIII(ImP)2]+, which led to a claim of dual (MLCT and LMCT) emission. Revisiting the photophysics of [FeIII(ImP)2]+, we confirmed however that higher (2MLCT) states of [FeIII(ImP)2]+ are short-lived (<10 ps) and therefore, in contrast to the previous interpretation, cannot give rise to emission on the nanosecond timescale. Accordingly, pristine [FeIII(ImP)2]+ prepared by us only shows red emission from its lower 2LMCT state (740 nm, 240 ps). The long-lived, higher energy emission previously reported for [FeIII(ImP)2]+ is instead attributed to an impurity, most probably a photoproduct of the Fe(ii) precursor. The previously reported emission quenching on the nanosecond time scale hence does not support any excited state reactivity of [FeIII(ImP)2]+ itself.

Human Gut Microbiome: A New Frontier in Cancer Diagnostics & Therapeutics.

The field of oncology is vast and ever-growing. The present cancer therapeutics is continually exhibiting various drawbacks, which opens the door for exploring better novel therapeutic techniques. One such emerging technique is the manipulation of gut microbiota to induce a positive curative effect in the body. The dynamic gut microbiota of our body houses an astonishing number of microorganisms, mainly bacteria. The balance of the gut microbiota is essential for good health as imbalances may result in dysbiosis leading to various diseases such as cancer. The gut microbiota can be manipulated by using prebiotics, probiotics, synbiotics, postbiotics, and antibiotics for better therapeutic outcomes, as well as to improve the quality of life of patients undergoing conventional cancer treatment. Administration of bacteria as a probiotic agent accompanied with prebiotics obtained from a wide variety of herbs has been used effectively to enhance the treatment of various cancers. Although the theoretical basis of Gut therapy can be ascertained, further clinical trials will be essential to determine the scope and limitations fully. The present review provides a glimpse of conventional and novel cancer therapeutics and their drawbacks, along with the role of the gut microbiome and its modulation to design new pharmaceutics against cancer.

4-Aminoquinoline derivatives: Synthesis, in vitro and in vivo antiplasmodial activity against chloroquine-resistant parasites.

Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives and found them to be effective against Plasmodium falciparum under in vitro conditions. Further, we selected four most active derivatives 1m, 1o, 2c and 2j and evaluated their antimalarial potential against Plasmodium berghei in vivo. These 4-aminoquinolines cured BALB/c mice infected with P. berghei. The ED50 values were calculated to be 2.062, 2.231, 1.431, 1.623 and 1.18 mg/kg of body weight for each of the compounds 1m, 1o, 2c, 2j and amodiaquine, respectively. Total doses of 500 mg/kg of body weight were well received. The study suggests that these new 4-aminoquinolines should be used for structure activity relationship to find lead molecules for treating multidrug-resistant Plasmodium falciparum and Plasmodium vivax.

Epidemiology and outcomes of Stenotrophomonas maltophilia and Burkholderia cepacia infections among trauma patients of India: a five year experience.

BACKGROUND: Infections by uncommon non-fermenting Gram negative bacteria are on the rise, but little is known about the risk factors and drug resistance in trauma patients in India. This study explored the infections caused by Stenotrophomonas maltophilia and/or Burkholderia cepacia in trauma patients over a period of 5 years. MATERIAL AND METHODS: Patients admitted for trauma care with S. maltophilia and/or B. cepacia isolated from clinical specimens were enrolled. Characteristics regarding the strain isolation, drug sensitivity pattern, multidrug resistance (MDR), patient, outcomes, and differentiation of true infection from colonisation were observed. RESULTS: Of the total 233 isolates, 102 were S. maltophilia and 131 were B. cepacia; 4.3% were responsible for polymicrobial infections with other bacteria. There were more B. cepacia MDR isolates than S. maltophilia. Maximum resistance was found to tetracycline (86.7%) and tobramycin (86.7%) in B. cepacia and to co-trimoxazole (68.7%) in S. maltophilia. Of these, 21 (16.03%) had a fatal outcome and the remaining 111 (84.7%) were discharged healthy. The in-hospital mortality rate associated with B. cepacia was much (16%) higher than S. maltophilia (13%) at this centre. CONCLUSION: The analysis of epidemiology and outcome of these infections will help to inform their management and treatment.

Increased preoperative collection of autologous blood with recombinant human erythropoietin therapy in tertiary care hospitals of Jammu.

INTRODUCTION: To study whether the administration of recombinant human erythropoietin increases the amount of autologous blood that can be collected before orthopaedic surgery. MATERIALS AND METHODS: We conducted a randomized controlled trial of recombinant human erythropoietin in 68 adults scheduled for elective orthopedic procedures. The patients received either erythropoietin 600 units/kg of body weight or placebo intravenously every 5(th) day prior to each phlebotomy for 21 days during which time up to 5 units of blood was collected. Patients were excluded from donation when their hematocrit values were less than 33%. All patients received iron sulphate 325mg orally 3 times daily. The mean number of units collected per patient was 4.33 ± 0.4 for erythropoietin group and 3.05± 0.71 for the placebo group. RESULTS: The mean packed red cell volume donated by patients who received erythropoietin was 32% greater than that donated by patients who received placebo (196.3 vs. 169.4 ml, p<0.05). 68% in the placebo group and 9% of patients treated with erythropoietin were unable to donate ≥4 units. No adverse effects were attributed to erythropoietin. While participating in the study, complications developed in 2 patients one in each group necessitating their removal from the study. CONCLUSION: We conclude that recombinant human erythropoietin increases the ability of the patients about to undergo elective surgery to donate autologous blood units.