In vivo capture of bacterial cells by remote guiding

Recently, it has been shown that several bacterial strains can be very efficient in cancer treatment since they possess many important properties such as self-targeting, ease of detection, sensing and toxicity against tumors. However, there are only a few relevant candidates for such an approach, as targeting and detection one of the biggest challenges as well as there are many limitations in the use of genetic approaches. Here, it is proposed the solution that enables surface modification of alive bacterial cells without interfering with their genetic material and potentially reduces their toxic side effect. By the electrostatic interaction fluorescently labeled polyelectrolytes (PEs) and magnetite nanoparticles (NPs) were deposited on the bacterial cell surface to control the cell growth, distribution and detection of bacteria. According to the results obtained in vivo, by the magnet entrapment of the modified bacteria the local concentration of the cells was increased more than 5 times, keeping the high concentrations even when the magnet is removed. Since the PEs create a strong barrier, in vitro it was shown that the division time of the cells can be regulated for better immune presentation.

Amelioration of 5-fluorouracil-induced intestinal mucositis by Streptococcus thermophilus ST4 in a mouse model

Intestinal mucositis is a commonly encountered toxic side effect in patients undergoing 5-fluorouracil (5-FU)-based chemotherapy. Numerous studies have shown that probiotics enable improving chemotherapy-induced intestinal mucositis, but the beneficial effects of probiotics differ depending on the strain. Therefore, in the present studies we suggest that S. thermophilus ST4 separated from raw milk may assess mucoprotective activity in 5-FU-induced intestinal mucositis. In our causal-comparative study design, fifteen mice were randomized assigned into three groups (n = 5/each group): control group, 5-FU group and 5-FU+S. thermophilus ST4 group. The control group was orally administrated saline only, and the 5-FU group was followed by intraperitoneal injection of 5-FU for 3 days after 10-day saline administration, and the 5-FU+S. thermophilus ST4 group was intragastrically subjected for S. thermophilus ST4 once per day during the whole experiment, starting from the first day of the experiment, followed by 5-FU intraperitoneal injection for 3 days after 10-day S. thermophilus ST4 pretreatment. Diarrhea score, pro-inflammatory cytokines serum levels, intestinal histopathology and short chain fatty acid were assessed. Here, we demonstrated the beneficial effects of S. thermophilus ST4 derived from raw milk against 5-FU-induced intestinal mucositis, including body weight reduction, appetite loss and diarrhea. Intrinsically, S. thermophilus ST4 effectively maintained epithelium structure in small intestines and colons as well as reduced the intestinal inflammation. Besides, S. thermophilus ST4 significantly increased the expression of acetic acid, reinforcing the muco-protective effects. In conclusion, our results demonstrate that S. thermophilus ST4 supplementation ameliorates 5-FU-induced intestinal mucositis. This suggests probiotic may serve as an alternative therapeutic strategy for the prevention or management of 5-FU-induced mucositis in the future.

Synthesis of Carboxymethyl Starch-Bio-Based Epoxy Resin and their Impact on Mechanical Properties

In the current research, we observed numerous suggestions are promoting the use of bio-based epoxy resins, replacing the petroleum-based products like Diglycidyl ether of bisphenol A type epoxy resin DGEBA. With the passage of time, the impending challenges include preparation of environmentally-friendly epoxy with minimum toxic side effect and improved properties. Therefore, we describe a very useful method for preparing new silicone-bridged dimethyl siloxane monomers in high quantity, derived from naturally occurring eugenol. By putting the methyl siloxane, computed with different chain lengths into their molecular backbone. Such epoxy monomers have different molecular structure with high purity. This dimethyl siloxane epoxy, with lower viscosity than commercial DGEBA epoxy, has superior thermal properties, which were evaluated using differential scanning calorimetry DSC. Modification of CMS increases the hydrophilicity. Bio-based epoxy (self-prepared) resin improved adhesive properties, with the help of modified CMS. This study presents a very easy and effective chemical modification to enhance interfacial adhesion composites with superior properties.

Role of omega 3 fatty acid in chemo-therapy induced cognitive decline

Dear Madam, One of the toxic side effect of chemotherapeutic agents in the brain, now more frequently encountered due to a rising number of cancer survivors who recieved chemo, is chemo induced cognitive decline, known more popularly in clinics as chemobrain or chemofog (1). Cancer-related cognitive impairment (CRCI) is encountered in survivors of chemotherapy treated central nervous system and non central nervous system malignancies (1). CRCI can happen any time during and after the chemo (2). CRCI affects the executive function, memory, attention, concentration, language, processing speed and other domains of cognition culminating in reduced treatment compliance, poorer quality of life and ultimately decreased life span (2). Continuous...

Puerarin: A Review on the Pharmacological Activity, Chemical Properties and Pharmacokinetics of Main Isoflavonoid

: Conventional drugs as a means of alternative medicines have been in use in Asian and African nations and some developed countries for the treatment of ailment and curing of diseases. Objective: Puerarin a naturally occurring isoflavone in numerous plants is one of the conventional medications that possess anti-inflammatory and immunoregulatory properties for the treatment of cardiac illnesses, osteonecrosis, Parkinson’s ailments, Alzheimer’s disorders, and other circulatory and cardiac conditions. Puerarin is extensively distributed in numerous organs comprising the kidney, mammary gland, femur, tibia, stomach, liver, pancreas, brain, and lungs but at a low rate because of its poor availability. However, when co-administered with compounds like gastrodin that can covey it into the cell, it shows a wide range of pharmacological properties including antioxidant, antidiabetic, antimicrobial, antiviral, anti-inflammatory, anticancer, anti-Alzheimer, hepatoprotective, and neuroprotective activity. The biotransformation process of puerarin showed that is well metabolized with daidzein being the main hydrolyzed product. Puerarin is well tolerated in the body and dosage of up to 250 mg/kg per day does not initiate any toxic side effect but rather sows a wide range of its beneficial and pharmacological properties.

Sex-specific classification of drug-induced Torsade de Pointes susceptibility using cardiac simulations and machine learning

Torsade de Pointes (TdP), a rare but lethal ventricular arrhythmia, is a toxic side effect of many drugs. To assess TdP risk, safety regulatory guidelines require quantification of hERG channel block in vitro and QT interval prolongation in vivo for all new therapeutic compounds. Unfortunately, these have proven to be poor predictors of torsadogenic risk, and are likely to have prevented safe compounds from reaching clinical phases. While this has stimulated numerous efforts to define new paradigms for cardiac safety, none of the recently developed strategies accounts for patient conditions. In particular, despite being a well-established independent risk factor for TdP, female sex is vastly underrepresented in both basic research and clinical studies, and thus current TdP metrics are likely biased toward the male sex. Here, we apply statistical learning to synthetic data, generated by simulating drug effects on cardiac myocyte models capturing male and female electrophysiology, to develop new sex-specific classification frameworks for TdP risk. We show that (1) TdP classifiers require different features in females vs. males; (2) malebased classifiers perform more poorly when applied to female data; (3) female-based classifier performance is largely unaffected by acute effects of hormones (i.e., during various phases of the menstrual cycle). Notably, when predicting TdP risk of intermediate drugs on female simulated data, male-biased predictive models consistently underestimate TdP risk in women. Therefore, we conclude that pipelines for preclinical cardiotoxicity risk assessment should consider sex as a key variable to avoid potentially lifethreatening consequences for the female population.

Severe Pancytopenia Following Single Dose Methotrexate In Psoriasis: A Rare And Potentially Lethal Manifestation

: Methotrexate is an antimetabolite anticancer drug frequently used in the treatment of extensive chronic plaque psoriasis. Psoriatic plaque erosion is a rare toxic side effect of single-dose methotrexate and is described as a sign of the impending pancytopenia. Here, we report a case of a 48-year-old male, presented with multiple oral and genital erosions, fissuring over palm and soles for 5 days. His laboratory tests revealed severe pancytopenia and nephropathy. He had a history of chronic plaque psoriasis for which he took a single dose of 15 mg methotrexate. During the hospital stay, the patient needed folate antagonist, granulocyte colony stimulating factor (G-CSF), intravenous fluids, blood transfusions, and platelet transfusions. He recovered within 12 days of admission.

Synthesis and Cytotoxic Activity of Azine Derivatives of 6-Hydroxyxanthanodiene

Background: The conjugates of the sesquiterpene lactone of the eremophilane series of 6- hydroxyxanthanodiene with hydrogenated azines (piperidines and piperazines) have been synthesized and identified by NMR spectrometer. Objective: A lactone with an unusual skeleton “6-hydroxyxanthanodiene” was extracted from the plant Elecampane (Inula helenium L) and identified various species with NMR spectrometer. Methods: The cytotoxic, mitochondrial, and antioxidant activities on different tumor lines such as A549, HCT116, RD and Jurkat were investigated and determined possible mechanisms. Results: The results showed that the most potent compound was IIIi exhibiting highest cytotoxicity against RD cells (IC50 25.23 ± 0.04 μM), depolarized the mitochondrial membrane and was an effective antioxidant (IC50 inhibition of LP 10.68 ± 3.21 μM) without any toxic side effect on healthy cells. Conclusion: The conjugates of sesquiterpene lactone 6-hydroxyxanthanodiene III and hydrogenated azines may help to design potential promising anticancer drugs.

NUDT15 polymorphism explains serious toxicity to azathioprine in Indian patients with chronic immune thrombocytopenia and autoimmune hemolytic anemia: a case series

ObjectivesAzathioprine (AZA) is a commonly used immunosuppressant in patients with autoimmune diseases. The toxic side effect to AZA (myelosuppression, hair loss, and oral ulcers) are highly unpredictable which can be life threatening if not identified earlier and dose adjustments made or the drug is withdrawn.Case presentationHere we report a case series of five patients with severe toxicity while on treatment with AZA for autoimmune hemolytic anemia (n=1) and Immune thrombocytopenia (n=4). The common thiopurine methyltransferase (TPMT) variants (TPMT*2, *3A, *3B) were not present in these patients. However, all these patients had the NUDT15 415C>T variant that has been reported to explain serious toxicity to thioguanine in Asian patients.ConclusionsOur report suggests pre-emptive genotype-based dosing of AZA could reduce adverse toxicity and hence better outcome.