Background:Piper nigrum (PN) is well known for its cytotoxic and pharmacological benefits. However, there is minimal documented evidence about its cytotoxic efficacy against colorectal carcinoma. We therefore sought to procure a precisely quantitative and qualitative result, pertaining the efficacy of an ethanolic extract of PN (EEPN) against colorectal carcinoma.Materials and Methods:EEPN was prepared by subjecting dried PN seeds to gradient ethanol fractionation. The total phenol content (TPC), antioxidant activity (AOA), and anti-inflammatory activity (AIA) were determined using Folin–Ciocalteu assay, ferric reducing ability of plasma and 2, 2-diphenyl-1-picrylhydrazyl methods, and human red blood cells membrane stabilizing assay, respectively. Colorectal carcinoma cell lines (HCT-116, HCT-15, and HT-29) were procured from National Centre for Cell Science, Pune, and were cultured in Dulbecco's modified eagle media supplemented with 10% fetal bovine serum and 1 mM L-glutamine. Cells were seeded into a 96-well plate, followed by treatment with increasing concentrations of EEPN. The cytotoxic efficacy was evaluated based on percentage inhibition of cells, using sulforhodamine-B assay. The IC-50 values were calculated using Prism software (Prism from GraphPad software, Inc. CA, USA).Results:Biochemical analysis revealed that 50% EEPN exhibited higher TPC, AOA, and AIA when compared to 70% and 100% EEPN at any given concentration (P = 0.041). Cytotoxic analysis revealed a dose-dependent response with maximum cellular inhibition at TPC of 6 and 3 μg/ml, using 50% EEPN. However, 50% inhibition of cellular growth using 50% EEPN was seen with TPC of 3.2, 2.9, and 1.9 μg/ml at 24, 48, and 72 h, respectively, in HCT-15 cells. Hence, time- and dose-dependent increase in the cytotoxic efficacy of 50% EEPN against colorectal carcinoma cell lines were noted (P < 0.001).Conclusion:Given the significantly positive correlations exhibited between the biochemical and the cytotoxic properties evaluated in our study, we hereby conclude PN as a novel therapeutic spice for the treatment of colorectal carcinoma.

The levels of different molecules in the cell are rhythmically cycled by the molecular clock present at the cellular level. The circadian rhythm is closely linked to the metabolic processes in the cells by an underlying mechanism whose intricacies need to be thoroughly investigated. Nevertheless, Nrf2 has been identified as an essential bridge between the circadian clock and cellular metabolism and is activated by the by-product of cellular metabolism like hydrogen peroxide. Once activated it binds to the specific DNA segments and increases the transcription of several genes that play a crucial role in the normal functioning of the cell. The central clock located in the suprachiasmatic nucleus of the anterior hypothalamus synchronizes the timekeeping in the peripheral tissues by integrating the light-dark input from the environment. Several studies have demonstrated the role of circadian rhythm as an effective tumor suppressor. Tumor development is triggered by the stimulation or disruption of signaling pathways at the cellular level as a result of the interaction between cells and environmental stimuli. Oxidative stress is one such external stimulus that disturbs the prooxidant/antioxidant equilibrium due to the loss of control over signaling pathways which destroy the bio-molecules. Altered Nrf2 expression and impaired redox balance are associated with various cancers suggesting that Nrf2 targeting may be used as a novel therapeutic approach for treating cancers. On the other hand, Nrf2 has also been shown to enhance the resistance of cancer cells to chemotherapeutic agents. We believe that maximum efficacy with minimum side effects for any particular therapy can be achieved if the treatment strategy regulates the circadian rhythm. In this review, we discuss the various molecular mechanisms interlinking the circadian rhythm with the Nrf2 pathway and contributing to breast cancer pathogenesis, we also talk about how these two pathways work in close association with the cell cycle which is another oscillatory system, and whether this interplay can be exploited to overcome drug resistance during chemotherapy.

No abstract

No abstract

Pregnancy with an autoimmune disorder is faced with several risks for mother and fetus. The aim of the present study is to analyze the course and outcome of pregnancy in women with autoimmune disorders (AIDs). MethodsA retrospective cohort study was conducted at a tertiary care teaching hospital. The hospital records of 153 pregnancies with autoimmune disorders and 1095 low-risk pregnant women who served as controls were reviewed. An adverse perinatal outcome was defined as the presence of any obstetric complications, including preeclampsia, eclampsia, abruption, antepartum hemorrhage (APH), prematurity, fetal growth restriction (FGR), intrauterine death (IUD), intrapartum event, mode of delivery, birth weight, neonatal intensive care unit (NICU) stay, or disease-specific neonatal complications. For all statistical tests with twotailed probability, p<0.05 was considered statistically significant. ResultsA high incidence of adverse perinatal outcomes was observed in all women with AIDs when compared with age-matched controls. The highest incidence of adverse perinatal outcomes was observed in women with Takayasu's arteritis. The incidence of abortions was more in women with antiphospholipid antibody syndrome (APS) and Grave's disease (22.2% and 33.3%, respectively). The incidence of prematurity, fetal growth restriction (FGR), and low birth weight were highest in women with systemic lupus erythematosus (SLE). Pregnancy with myasthenia gravis and rheumatoid arthritis did not have any significant adverse impact on pregnancy outcomes. ConclusionWe found a strong association between autoimmune disorders and obstetric complications. The multidisciplinary team approach and pre-pregnancy optimization of the disease improve maternal and fetal outcomes.

No abstract

BackgroundIn a low-resource and high-volume setting, it is often felt that patient care cannot be improved within the limitations of existing infrastructure and resources. However, the use of a systematic problem-solving method can bring about significant improvement even in these settings.AimTo decrease the mean waiting time from first visit to initiation of infertility treatment by 70% within 4 weeks (1–30 June 2019) for patients coming to the gynaecological outpatient department (OPD).MethodsWe constructed a multidisciplinary quality improvement team consisting of an academic consultant, a senior resident physician, a junior resident physician and a nurse to address the problem of long waiting times to initiation of fertility treatment. We collected baseline data from 10 consecutive women presenting to gynaecological OPD with complaints of infertility by calculating the time between their first visit to the facility and the day of performance of hysterosalpingography (HSG). The average waiting time was found to be 6 months and 25 days (mean=6.85 months; 3.5–10 months). The team used process flow diagrams and fishbone analysis to identify various causes of these long waiting times. The main reason for the delay in starting infertility treatment was that the date for HSG was given only after seeing the endometrial aspiration report (ie, after ruling out endometrial tuberculosis as there is a risk of dissemination of tuberculosis during HSG). Also, HSG was done only once a week during a short 2-hour slot in the fluoroscopy room.ResultsAfter the implementation of change ideas, there was significant reduction in the waiting period to starting treatment in patients with infertility. After the first change idea, the average waiting period seen in 10 consecutive patients with infertility reduced to 3.25 months, that is, by 51.8% from baseline within a 2-week interval, and there is shift in the run chart diagram. After the second change idea, the waiting time reduced to 2 months, that is, by 70%, seen in the next 10 consecutive patients with infertility within the next 2 weeks’ time. The results were sustained to the average waiting time of 2 months for 6 months without any additional resources.ConclusionWith a well-organised and conducted quality improvement project and team efforts, the required changes can be brought about in an established conventional healthcare delivery system and improvements can be sustained over a long period of time.

No abstract