ß-Amyloid peptide modulates peripheral immune responses and neuroinflammation in rats.

Alzheimer's disease (AD) is characterized by immune system dysregulation, impacting both central and peripheral immune responses. The study aimed to investigate the mechanism behind the neurotoxic effects of ß-amyloid (Aß) peptide in the rat brain including the study of neuroinflammation, neurodegeneration, and alterations in peripheral immune responses (PIR). The neuroinflammation brought on by Aß1-42 and is unknown to influence PIR. Animal models were prepared, after 28 days, control, sham, and treated rats were anaesthetized and inflammatory markers of hippocampus and serum levels (reactive oxygen species, nitrite, tumor necrosis factor-α, and interleukin-1ß), and some markers of PIR (splenic mononuclear cells or MNC, cytotoxicity and phagocytic index of the white blood cells leukocyte adhesion inhibition index or LAI), as well as polymorphonuclear cells of the spleen, were assessed. In addition to changes in peripheral immune responses, the present study found that AD rats had higher blood levels of inflammatory markers. Based on the study, the immune system irregularities observed in AD rats in the peripheral regions might be connected to neuroinflammation, which is facilitated by a compromised blood-brain barrier. Hence, it is viable to propose that the neuroinflammatory condition in rats with Aß-induced AD could modify immune responses in the peripheral areas with significantly higher levels of inflammatory cytokines markers in the hippocampal tissue in Aß-injected AD rats.

Polycystic ovary syndrome and its management: In view of oxidative stress.

In the past two decades, oxidative stress (OS) has drawn a lot of interest due to the revelation that individuals with many persistent disorders including diabetes, polycystic ovarian syndrome (PCOS), cardiovascular, and other disorders often have aberrant oxidation statuses. OS has a close interplay with PCOS features such as insulin resistance, hyperandrogenism, and chronic inflammation; there is a belief that OS might contribute to the development of PCOS. PCOS is currently recognized as not only one of the most prevalent endocrine disorders but also a significant contributor to female infertility, affecting a considerable proportion of women globally. Therefore, the understanding of the relationship between OS and PCOS is crucial to the development of therapeutic and preventive strategies for PCOS. Moreover, the mechanistic study of intracellular reactive oxygen species/ reactive nitrogen species formation and its possible interaction with women's reproductive health is required, which includes complex enzymatic and non-enzymatic antioxidant systems. Apart from that, our current review includes possible regulation of the pathogenesis of OS. A change in lifestyle, including physical activity, various supplements that boost antioxidant levels, particularly vitamins, and the usage of medicinal herbs, is thought to be the best way to combat this occurrence of OS and improve the pathophysiologic conditions associated with PCOS.

A Randomized Controlled Trial Comparing Remission Induction with Modified Multitarget Therapy with Intravenous Cyclophosphamide in Proliferative Lupus Nephritis.

Introduction: Therapy of proliferative lupus nephritis (PLN) is yet to be optimized. Standard of care for induction consists of intravenous (IV) cyclophosphamide (CYC) and steroids, which shows an improved outcome, but end-stage renal disease (ESRD) progression, increased mortality, and therapy-related adverse effects remain a major concern. The other treatment reported to induce early remission was the multitarget therapy comprising tacrolimus, mycophenolate, and steroid, but infections were high in the multitarget therapy. Considering azathioprine as a potentially safer and effective alternative anti-B-cell therapy, modified multitarget therapy (MMTT) was planned replacing mycophenolate with azathioprine. Material and Methods: A single-center, 24-week, open-label, randomized controlled trial comprising adults of age 18-65 years with biopsy-proven PLN was carried out. The intervention groups were 1) MMTT: tacrolimus 0.075 mg/kg/day and azathioprine 2 mg/kg/day and 2) IV CYC group with a starting dose of 0.75 (adjusted to 0.5-1.0) g/m2 every 4 weeks for 6 months. Both groups received 3 days of pulse methylprednisolone followed by a tapering course of oral prednisone therapy. Results: Among 100 randomized patients, 48 were in MMTT arm and 52 were in IV CYC arm. At the end of 24 weeks, overall remission (complete and partial) was comparable in both the arms: MMTT (86.36%) and IV CYC (87.75%). There was comparable proteinuria reduction and systemic lupus erythematosus disease activity index (SLEDAI) score improvement with recovery of complement level C3 in both groups. Major adverse events were numerically more in the IV CYC group, including one death from pneumonia. Conclusion: The MMTT arm is as effective as IV CYC in improving short-term outcome in PLN, with a comparable safety profile.

Beyond traditional therapy: Mucoadhesive polymers as a new frontier in oral cancer management.

In recent times mucoadhesive drug delivery systems are gaining popularity in oral cancer. It is a malignancy with high global prevalence. Despite significant advances in cancer therapeutics, improving the prognosis of late-stage oral cancer remains challenging. Targeted therapy using mucoadhesive polymers can improve oral cancer patients' overall outcome by offering enhanced oral mucosa bioavailability, better drug distribution and tissue targeting, and minimizing systemic side effects. Mucoadhesive polymers can also be delivered via different formulations such as tablets, films, patches, gels, and nanoparticles. These polymers can deliver an array of medicines, making them an adaptable drug delivery approach. Drug delivery techniques based on these mucoadhesive polymers are gaining traction and have immense potential as a prospective treatment for late-stage oral cancer. This review examines leading research in mucoadhesive polymers and discusses their potential applications in treating oral cancer.

Optimization of estrogen dosage for uterine receptivity for implantation in post-coital bilaterally ovariectomized mice.

Estrogens and progesterone, in unison and/or separately, synchronize the distinct events of blastocyst development, uterine priming and receptivity induction for implantation. In contrast to high implantation failure rates, the mechanistic concepts regarding the uterine receptivity for implantation still remain elusive. The present study aims to define the minimum estradiol (E2) dose to induce uterine receptivity for successful implantation in post-coitus bilaterally ovariectomized (BLO) progesterone-primed uterus of mice. Post-coital sperm-positive adult female mice were divided into two groups. In both the groups, delayed implantation was induced by BLO on post-coitus Day 4 (D4). Group 1 received 2 mg of progesterone (P4) from D5 until sacrifice, and E2 injection of 3.0, 10.0, 25.0 and 50.0 ng on D7. On D8, all mice of this group were sacrificed except the mice that received second dose of 25.0 ng of E2 on D8 and were sacrificed on D9. Group 2 followed the same doses, but were given simultaneously on D4, and sacrificed on D5. The mice that received second doses of 25.0 ng E2 were sacrificed on D6. The minimum dose of E2 required to induce uterine receptivity for implantation is a single dose of 50.0 ng E2. The uterus remained refractory following short receptive period at E2 doses lower than 50.0 ng, which is just sufficient to establish desired uterine receptivity. However, repeated administration of sub-threshold doses of 25.0 ng of E2 could also not effectively sustain uterine receptivity towards successful implantation.

Glycopolymer Decorated pH-Dependent Ratiometric Fluorescent Probe Based on Förster Resonance Energy Transfer for the Detection of Cancer Cells.

Development of fluorescent imaging probes is an important topic of research for the early diagnosis of cancer. Based on the difference between the cellular environment of tumor cells and normal cells, several "smart" fluorescent probes have been developed. In this work, a glycopolymer functionalized Förster resonance energy transfer (FRET) based fluorescent sensor is developed, which can monitor the pH change in cellular system. One-pot sequential reversible addition-fragmentation chain transfer (RAFT)polymerization technique is employed to synthesize fluorescent active triblock glycopolymer that can undergo FRET change on the variation of pH. A FRET pair, fluorescein o-acrylate (FA) and 7-amino-4-methylcoumarin (AMC) is linked via a pH-responsive polymer poly [2-(diisopropylamino)ethyl methacrylate] (PDPAEMA), which can undergo reversible swelling/deswelling under acidic/neutral condition. The presence of glycopolymer segment provides stability, water solubility, and specificity toward cancer cells. The cellular FRET experiments on cancer cells (MDA MB 231) and normal cells (3T3 fibroblast cells) demonstrate that the material is capable of distinguishing cells as a function of pH change.

Gold Nanoparticle Embedded Stimuli-Responsive Functional Glycopolymer: A Potential Material for Synergistic Chemo-Photodynamic Therapy of Cancer Cells.

Photodynamic therapy has emerged as a noninvasive treatment modality for several types of cancers. However, conventional hydrophobic photosensitizers (PS) suffer from low water solubility and poor tumor-targeting ability. Therefore, PS modified with glycopolymers can offer adequate water solubility, biocompatibility, and tumor-targeting ability due to the presence of multiple sugar units. In this study, a well-defined block copolymer poly(3-O-methacryloyl-d-glucopyranose)-b-poly(2-(4-formylbenzoyloxy)ethylmethacrylate) (PMAG-b-PFBEMA) containing pendant glucose and aldehyde units is synthesized via reversible addition-fragmentation chain transfer polymerization method. A water-soluble PS (toluidine blue O; TBO) and a potent anticancer drug, Doxorubicin (Dox) are introduced to the polymer backbone via acid-labile Schiff-base reaction (PMAG-b-PFBEMA_TBO_Dox). The PMAG-b-PFBEMA_TBO_Dox is then anchored on the surface of gold nanoparticles (AuNPs) via electrostatic interaction. This hybrid system exhibits excellent reactive oxygen species (ROS) generating ability under exposure of 630 nm light-emitting diode along with triggered release of Dox under the acidic pH of tumor cells. The in vitro cytotoxicity study on human breast cancer cell line, MDA MB 231, for this hybrid system shows promising results due to the synergistic effect of ROS and Dox released. Thus, this glycopolymer-based dual (chemo-photodynamic) therapy model can work as potential material for future therapeutics.

Waist-to-height ratio and BMI as predictive markers for insulin resistance in women with PCOS in Kolkata, India.

PURPOSE: Polycystic ovarian syndrome (PCOS) is most commonly presented with insulin resistance (IR). Simple anthropometric indices may serve as surrogate markers of these conditions with population-based cut-off values. The present study suggests the cut-off values of waist-to-height ratio (WHtR) and body mass index (BMI) in early prediction of PCOS and IR in PCOS women based in Kolkata, a major metropolitan city in India. METHODS: This cross-sectional study included 66 women (aged 16-30 years) from Kolkata, India, with confirmed PCOS, using Rotterdam criteria. IR was defined following the homeostasis model assessment (HOMA). Anthropometric and biochemical data were obtained using standard protocol and compared among the PCOS subjects grouped as per IR prevalence, BMI, and WHtR values. The receiver operating characteristics (ROC) curve was applied to evaluate and compare the cut-off values of WHtR and BMI in the prediction of PCOS and IR in women with PCOS. RESULTS: As per ROC analysis, WHtR showed significantly higher AUC in the detection of PCOS and IR in PCOS subjects respectively, than that of BMI. The cut-off values of WHtR and BMI for PCOS were 0.560 and 28.47 respectively, and for IR in PCOS patients, were 0.620 and 29.14 respectively. CONCLUSIONS: The present study suggests a cut-off value of WHtR to be used as an inexpensive and noninvasive screening tool for early prediction of PCOS and IR among PCOS afflicted women based in Kolkata, India and for this prediction, the study also claims WHtR as a better index than BMI.

REDOX Responsive Fluorescence Active Glycopolymer Based Nanogel: A Potential Material for Targeted Anticancer Drug Delivery.

A well-defined glycopolymer based fluorescence active nanogel has been prepared via the combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and Diels-Alder (DA) "click" chemistry. To prepare the nanogel, initially, a functional AB block copolymer (BCP) poly(pentafluorophenyl acrylate)-b-poly(furfuryl methacrylate) (PPFPA-b-PFMA), having activated pentafluorophenyl ester group, was synthesized via RAFT polymerization. The activated pentafluorophenyl functionality was replaced by the amine functionality of glucosamine to introduce the amphiphilic BCP poly[2-(acrylamido) glucopyranose]-b-poly(furfuryl methacrylate) (PAG-b-PFMA). Furthermore, the terminal acid (-COOH) functionality of the RAFT agent was modified by gelatin QDs (GQDs) to generate fluorescence active glycopolymer. An anticancer drug, Doxorubicin, was loaded in the micelle via the successive addition of the drug molecule and cross-linking using dithio-bismaleimidoethane (DTME), a REDOX responsive cross-linker. The anticancer activity of the drug loaded nanogel was observed over MBA-MD-231, human breast cancer cell line, and monitored via fluorescence spectroscopy and flow cytometric analyses (FACS). The cytotoxicity of the prepared glycopolymer based nanogel over the MBA-MD-231 cell line was assessed via MTT assay test, and it was observed that the synthesized nanogel was noncytotoxic in nature.

Effect of Alocasia indica tuber extract on reducing hepatotoxicity and liver apoptosis in alcohol intoxicated rats.

The possible protective role of ethanolic extract of A. indica tuber (EEAIT) in hepatotoxicity and apoptosis of liver caused by alcohol in rats was investigated. Treatment of rats with alcohol (3 g ethanol per kg body weight per day for 15 days intraperitoneally) produced marked elevation of liver biomarkers such as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GT), and total bilirubin levels which were reduced by EEAIT in a dose-dependent manner. Furthermore, EEAIT improved antioxidant status (MDA, NO, and GSH) and preserved hepatic cell architecture. Simultaneous supplementation with EEAIT significantly restored hepatic catalase (CAT) and superoxide dismutase (SOD) activity levels towards normal. The studies with biochemical markers were strongly supported by the histopathological evaluation of the liver tissue. EEAIT also attenuated apoptosis and necrosis features of liver cell found in immunohistochemical evaluation. HPLC analysis of the extract showed the presence of three major peaks of which peak 2 (RT: 33.33 min) contains the highest area (%) and UV spectrum analysis identified it as flavonoids. It is therefore suggested that EEAIT can provide a definite protective effect against chronic hepatic injury caused by alcohol in rats, which may mainly be associated with its antioxidative effect.

Male reproductive health and yoga.

Now-a-days reproductive health problems along with infertility in male is very often observed. Various Assisted Reproductive Technologies have been introduced to solve the problem, but common people cannot afford the cost of such procedures. Various ayurvedic and other alternative medicines, along with regular yoga practice are proven to be not only effective to enhance the reproductive health in men to produce a successful pregnancy, but also to regulate sexual desire in men who practice celibacy. Yoga is reported to reduce stress and anxiety, improve autonomic functions by triggering neurohormonal mechanisms by the suppression of sympathetic activity, and even, today, several reports suggested regular yoga practice from childhood is beneficial for reproductive health. In this regard the present review is aimed to provide all the necessary information regarding the effectiveness of yoga practice to have a better reproductive health and to prevent infertility.

Ovulation and rate of implantation following unilateral ovariectomy in mice.

OBJECTIVES: Removal of an ovary of any side of the body is called the unilateral ovariectomy (ULO). ULO models are used to analyze the existence of functional and physiological asymmetries between the ovaries, including the ovum implantation. MATERIALS AND METHODS: ULO was done in mice without any specification on their stages of the estrous cycle. The animals were mated between 3(rd) and 15(th) day after ULO to observe the consequence of ULO on ovulation and ovum implantation. RESULTS: Ovulation and number of implantation were decreased in proportion to single contralateral ovary if the animals were mated within 36 hrs of ULO. It resulted in increased weight of contralateral ovary due to hypertrophy, and also in compensatory ovulation, formation of corpus luteum (CL) that reached a peak after 14(th) and 15(th) day of ULO (sacrificed on 5(th) day of pregnancy i.e., 19(th) and 20(th) day of ULO) compared to animals undergone sham-surgery. Numbers of implantations were also increased progressively on the contralateral ovarian side and get to a peak after similar days of compensation. DISCUSSION AND CONCLUSION: Following ULO, the remaining ovary started to compensate within 5(th) to 6(th) day of ULO even during pregnancy. Ovarian histology also showed increased formation of CL which is a marker of rate of ovulation.