Placental exosomes in pregnancy and preeclampsia.

Preeclampsia, poses significant risks to both maternal and fetal well-being. Exosomes released by the placenta play a crucial role in intercellular communication and are recognized as potential carriers of essential information for placental development. These exosomes transport a payload of proteins, nucleic acids, and lipids that mirror the placental microenvironment. This review delves into the functional roles of placental exosomes and its contents shedding light on their involvement in vascular regulation and immune modulation in normal pregnancy. Discernible changes are reported in the composition and quantity of placental exosome contents in pregnancies affected by preeclampsia. The exosomes from preeclamptic mothers affect vascularization and fetal kidney development. The discussion also explores the implications of utilizing placental exosomes as biomarkers and the prospects of translating these findings into clinical applications. In conclusion, placental exosomes hold promise as a valuable avenue for deciphering the complexities of preeclampsia, providing crucial diagnostic and prognostic insights. As the field progresses, a more profound comprehension of the distinct molecular signatures carried by placental exosomes may open doors to innovative strategies for managing and offering personalized care to pregnancies affected by preeclampsia.

Clinical Utility of Sperm Function Tests in Predicting Male Fertility: A Systematic Review.

Routine semen analysis provides considerable information regarding sperm parameters; however, it is not solely adequate to predict male fertility potential. In the past two decades, several advance sperm function tests have been developed. The present systematic review intends to assess the clinical utility of available advance sperm function tests in predicting the male fertility potential. A systematic literature search was conducted as per PRISMA guidelines using PubMed, MEDLINE, Google Scholar, and Cochrane Library. Different keywords either singly or in combination were used to retrieve the relevant articles related to sperm function tests, male fertility, and pregnancy outcomes. A total of 5169 articles were obtained, out of which 110 meeting the selection criteria were included in this review. The majorly investigated sperm function tests are hypo-osmotic swelling test, acrosome reaction test, sperm capacitation test, hemizona binding assay, sperm DNA fragmentation test, seminal reactive oxygen species test, mitochondrial dysfunction tests, antisperm antibody test, nuclear chromatin de-condensation (NCD) test, etc. The different advance sperm function tests analyse different aspects of sperm function. Hence, any one test may not be helpful to appropriately predict the male fertility potential. Currently, the unavailability of high-quality clinical data, robust thresholds, complex protocols, high cost, etc., are the limiting factors and prohibiting current sperm function tests to reach the clinics. Further multi-centric research efforts are required to fulfil the existing lacunas and pave the way for these tests to be introduced into the clinics.

Diverse role of endocannabinoid system in mammalian male reproduction.

Endocannabinoid system (ECS) is known for its modulatory role in numerous physiological processes in the body. Endocannabinoids (eCBs) are endogenous lipid molecules which function both centrally and peripherally. The ECS is best studied in the central nervous system (CNS), immune system as well as in the metabolic system. The role of ECS in male reproductive system is emerging and the presence of a complete enzymatic machinery to synthesize and metabolize eCBs has been demonstrated in male reproductive tract. Endocannabinoid concentrations and alterations in their levels have been reported to affect the functioning of spermatozoa. A dysfunctional ECS has also been linked to the development of prostate cancer, the leading cause of cancer related mortality among male population. This review is an attempt to provide an insight into the significant role of endocannabinoids in male reproduction and further summarize recent findings that demonstrate the manner in which the endocannabinoid system impacts male sexual behavior and fertility.

Bacterial and archaeal diversity in oil fields and reservoirs and their potential role in hydrocarbon recovery and bioprospecting.

Hydrocarbon is a primary source of energy in the current urbanized society. Considering the increasing demand, worldwide oil productions are declining due to maturity of oil fields and because of difficulty in discovering new oil fields to substitute the exploited ones. To meet current and future energy demands, further exploitation of oil resources is highly required. Microorganisms inhabiting in these areas exhibit highly diverse catabolic activities to degrade, transform, or accumulate various hydrocarbons. Enrichment of hydrocarbon-utilizing bacteria in oil basin is caused by continuous long duration and low molecular weight hydrocarbon microseepage which plays a very important role as an indicator for petroleum prospecting. The important microbial metabolic processes in most of the oil reservoir are sulfate reduction, fermentation, acetogenesis, methanogenesis, NO3- reduction, and Fe (III) and Mn (IV) reduction. The microorganisms residing in these sites have critical control on petroleum composition, recovery, and production methods. Physical characteristics of heavy oil are altered by microbial biotransformation and biosurfactant production. Considering oil to be one of the most vital energy resources, it is important to have a comprehensive understanding of petroleum microbiology. This manuscript reviews the recent research work referring to the diversity of bacteria in oil field and reservoir sites and their applications for enhancing oil transformation in the target reservoir and geomicrobial prospecting scope for petroleum exploration.

Incidence of postoperative pain after single-visit and multiple-visit root canal therapy: A randomized controlled trial.

Background: Short-term complications after root canal therapy (RCT) include mild pain or flare-up. Patients regard these complications as a benchmark for the assessment of clinician's abilities. In this context, the evidence for recommending either one- or two-visit RCT is not consistent. Aims: This study aims to compare the prevalence of postoperative pain and tenderness to percussion after single-visit (SV) versus two-visit RCT on the mandibular first molar. Materials and Methods: The study was registered with www.ctri.nic.in (CTRI/2019/05/019067). Seventy individuals requiring RCT on a mandibular first molar were selected and randomly ascribed to either single- (Group 1, n = 35) or two-visit RCT (Group 2, n = 35). Postoperative pain levels were assessed using heft parker visual analog scale. The treated teeth were appraised for tenderness to percussion after 1 week of obturation. Statistical Analysis: Thirty-four patients were evaluated in each group: One patient, each, dropped out from both the groups. The data analysis was done using Student's t-test and Chi-square test. Results and Conclusion: Pain score in multiple-visit (MV) was significantly higher than SV after 12- (P = 0.039) and 48 h (P = 0.043). Short-term postoperative pain was higher in MV than SV RCT of mandibular first molar teeth.

p-Coumaric acid attenuates alcohol exposed hepatic injury through MAPKs, apoptosis and Nrf2 signaling in experimental models.

Overconsumption of alcohol could lead to severe liver injury that connects with oxidative stress, apoptosis, and inflammatory response. Previously, we proved that p-coumaric acid prevents ethanol induced reproductive toxicity; however, p-coumaric acid (PCA) on ethanol mediated hepatotoxicity has not been examined yet. In our work, we sought to study the potential of PCA in contradiction of ethanol induced hepatoxicity which linking with MAPKs, apoptosis, oxidative stress, and Nrf2 signaling. Foremost, we found that PCA could protect ethanol induced both L-02 and HepG2 hepatic cells by inhibiting cytotoxicity, ROS production, mitochondrial depolarization, and nuclear fragmentation. Also, in vivo experiments showed that the ethanol increasing the lipid markers (TBARS, CD) and depletes the antioxidants thereby increased phosphorylation of JNK, ERK, and p38 in rat liver tissues. Interestingly, PCA treatments inhibit ethanol exposed lipid markers and depletion of antioxidants, which directs the inhibition of MAPKs activation in rat liver tissues. We also noticed that the PCA protected ethanol induced apoptosis and liver markers by inhibiting the expression of Bax, caspases; AST, ALT, ALS, and LDH in liver tissue. Overall, the ameliorative consequence of PCA on ethanol induced oxidative stress and apoptosis was achieved by suppressing the expression of CYP2E1 and overexpressing Nrf2 and its target protein HO-1 in rat liver tissue. As a result, PCA was marked to be an effective antioxidant with notable hepatoprotection by inhibiting MAPKs and apoptosis signaling via enhancing Nrf2 signaling.

Primary Ewing's Sarcoma of Maxillary sinus: A Case Report.

Ewing's sarcoma are small round cell tumors belonging to Ewing's family of tumors and the second most common bone tumor seen in children. The most common affected sites are long bones of extremities followed by pelvis and ribs. Primary arising in head and neck region is uncommon and maxillary Ewing's sarcoma is rarely seen. Histologically it is one of many small round cell tumors found in children and therefore immunohistochemical and occasionally molecular studies are required to establish the diagnosis. Imaging features include aggressive bony destruction with periosteal reaction and associated soft tissue mass. Treatment of this tumor is a combination of induction chemotherapy followed by surgery and/or radiation with completion of chemotherapy due to aggressive nature and a high propensity for metastases. Our case is an 11year-old boy diagnosed with primary non-metastatic Ewing's sarcoma of left maxilla. The tumor was positive for CD 99 and FLI-1 and negative for CD 45 and Tdt on immuno-histocytochemical examination. The patient was treated with induction chemotherapy comprising of alternating 3 weekly cycles of Vincristine, Adriamycin and Cyclophosphamide with Etoposide and Ifosfamide. This was followed by radical conformal radiation to a dose of 55.8Gy in 31 fractions with good response. Keywords: Ewing's sarcoma, maxilla, IHC, chemotherapy, radiation.

p-Coumaric acid ameliorates ethanol-induced kidney injury by inhibiting inflammatory cytokine production and NF-κB signaling in rats

Objective: To examine the effects of p-coumaric acid on ethanol-induced kidney injury in Swiss Wistar rats. Methods: Ethanol (25％ v/v) was used to induce nephrotoxicity in rats. p-Coumaric acid was orally administered at 50, 100, or 200 mg/kg body weight. The levels of oxidative parameters were determined; pro-inflammatory biomarkers were analyzed by Western blotting and apoptotic protein was analyzed by immunohistochemistry. Results: Ethanol treated rats showed decreased levels of antioxidants and aberrant production of pro-inflammatory cytokines (IL-6, IL1β, TNF-α), NF-κB activation and imbalance of pro-and anti-apoptotic proteins (Bcl-2, Bax, caspase 3). Meanwhile, p-coumaric acid restored antioxidant levels and decreased the levels of inflammatory cytokines, NF-κB, and pro-apoptotic proteins and increased Bcl-2 expression. Conclusions: p-Coumaric acid ameliorates ethanol-induced kidney injury by restoring antioxidant production and suppressing cellular apoptosis and inhibiting NF-κB expression. p-Coumaric acid should be further investigated as a promising candidate for ethanol-induced kidney toxicity.

Protective effects of p­coumaric acid on ethanol induced male reproductive toxicity.

Alcohol, a psychoactive drug is one of the lifestyle factors responsible for male infertility. Present study was carried out to investigate the ameliorative effect of p­coumaric acid (PCA), a plant derived bioactive phenolic compound on alcohol induced chronic reproductive toxicity in male rats. Thirty male Wistar rats were divided into five groups, each with six animals. Group I as control received vehicle (distilled water) alone. And the following Group II, III, IV, V were treated orally with sequentially (per week) increased dose of ethanol 25% v/v (5, 8, 10 and 12 g/kg b wt per week in each group) for 28 days. On the 3rd and 4th week, the groups III, IV, V were administered with p­coumaric acid orally at three different concentrations (Low 50 mg/kg b wt; Medium 100 mg/kg b wt; High 200 mg/kg b wt). The rats treated with ethanol showed abnormal sperm characteristics, reduced anti-oxidant level, reduced testosterone level and abnormal testicular histoarchitecture while the rats treated with PCA in addition to ethanol were found to have protective effects on sperm parameters and apoptosis. The increased caspase-3, caspase-7, p21 immunoreactivity and reduced Cdk4 immunoreactivity in ethanol treated rats confirmed that ethanol increases the apoptosis in testis and a reduced expression in the rats treated with PCA in addition to ethanol indicates a protective role of PCA. Overall, our results showed that PCA mitigates alcohol induced male reproductive toxicity and improves reproductive health in male Wistar rats.

Identification of 2,4-dihydroxy-5-pyrimidinyl imidothiocarbomate as a novel inhibitor to Y box binding protein-1 (YB-1) and its therapeutic actions against breast cancer.

In spite of advances in breast cancer treatment and early diagnosis, drug toxicity, cancer relapse, multidrug resistance and metastasis are the major impediment to the developments of efficient drugs. However, unique druggable targets of cancer cells distinct from the normal cells provide new rationale in cancer treatment. Previous reports clearly emphasize the differential expression and localization of Y box binding protein-1 (YB-1) between normal breast tissues and different stages of breast cancer. Y box binding protein-1 is DNA as well as RNA binding protein involved in transcription and translation regulation of various proteins involved in cancer progression, apoptosis, cell cycle, epithelial to mesenchymal transition (EMT) and drug resistance. Particularly, during doxorubicin (DOX) treatment and cancer relapse conditions, YB-1 expression was very high in breast cancer tissues and localized in to nucleus which further favours DOX efflux and metastasis. Moreover, siRNA mediated silencing of YB-1 reduces breast cancer progression and metastasis. In this rationale, using an array of computational methods, 2,4-dihydroxy-5-pyrimidinyl imidothiocarbomate (DPI) has been screened out as a drug-likeness antagonist to the YB-1for cancer treatment. In this study, we determined that DPI was toxic to breast cancer cell lines as individual drug as well as in combination with DOX. Moreover, immunofluorescence and confocal studies showed that DPI decreases DOX induced YB-1 nuclear translocation and increases DOX accumulation in breast cancer cell line. A G1/G0 phase cell cycle arrest and apoptosis was also induced by DPI. Moreover, DPI modulated YB-1 downstream targets such as p53, caspase-3, CDK-1 which are involved in cell cycle progression and apoptosis. Further, metastatic functional analysis revealed that DPI inhibits cell adhesion, migration, invasion in aggressive metastatic cell line and inhibits angiogenesis in chick embryonic chorioallantoic membrane (CAM) model. Meanwhile, DPI alters the expression of YB-1 downstream targets which are involved in metastasis such as VEGFR, caveolin, E-cadherin, cytokeratins, desmin and vimentin in MDA-MB-231 xenograft in chick embryonic CAM membrane. The results clearly demonstrated that DPI inhibited YB-1 nuclear translocation, thereby exhibited anti-apoptotic, anti-proliferative and anti-metastatic activities and increases the therapeutic potential of commercial breast cancer drug doxorubicin.

Doxorubicin-induced female reproductive toxicity: an assessment of ovarian follicular apoptosis, cyclicity and reproductive tissue histology in Wistar rats.

Doxorubicin is a widely used chemotherapeutic agent for various cancers, particularly for the female breast cancer patients. Although the rate of young female cancer patients is increasing every year, conversely the lack of knowledge of adverse effects of doxorubicin on female reproductive system insisted us to assess the toxic effects of doxorubicin on the female reproductive tissue histoarchitecture, cyclicity, and mammary glands in Wistar rats. The rats were divided into two groups depending on the treatment period, i.e., 24 h and 28 d and further subdivided into three subgroups and administered with doxorubicin at 3 mg/kg bw (subgroup I), 6 mg/kg bw (subgroup II), and equal volume of normal saline (subgroup III) intraperitoneally once during the whole treatment period. We observed a significantly altered estrous cycle with a prolonged diestrous and short proestrous in higher dose group and dose-dependent significant changes in the uteri and mammary gland histoarchitecture in 28 days treated rats as compared to control. Moreover, the micronuclei and chromosomal aberration frequency were increased significantly in both treatment groups. A significant increase in follicular atresia in ovaries of the 28 days treated rats was observed. The immunohistochemical analysis of ovarian tissues showed an increased p53 and caspase 3 expression and apoptosis in primordial follicles of treated rats. The results suggest that though doxorubicin is a potential chemotherapeutic drug for many tumors, but the risk of adverse effects on the female reproductive system is there even at low doses.

Chlorpyrifos induced toxicity in reproductive organs of female Wistar rats.

Chlorpyrifos (CPF) is an organophosphate (OP) insecticide extensively used in agricultural and domestic settings. Healthy adult female albino rats were divided into three groups of six rats in each. Two groups were dosed orally with CPF in vegetable oil (0.1 and 2.5 mg/kg/day) and third group was given vegetable oil for 8 weeks. Non-significant changes were observed for body weight and feed intake. A disruption in estrous cyclicity was observed with a prolonged metestrous. Erythrocyte osmotic fragility and lipid peroxidation levels increased significantly. Mammary gland whole mounts revealed a significant (P<0.05-0.0001) increase in the ductal thickness, number of branches, alveolar and terminal end bud number and terminal end bud diameter. A significant increase in ovarian surface epithelium height, follicular diameter and follicular atresia was observed in treated rats (P<0.05-0.0001). A similar significant increase in the uterine surface epithelium height, endometrial gland epithelium height and myometrium thickness in higher dose group was recorded (P<0.05-0.0001). Luminal epithelium height and endometrial gland diameter was increased significantly in both the treated groups (P<0.05-0.0001). The results indicate that sub-chronic exposure of CPF causes oxidative stress and negative effects on the reproductive organs of female rats, which may be a pointer towards beginning of cancer incidence.