Phytochemical profiling, antioxidant potential and cytotoxic activity of Sargassum prismaticum extracts: implications for therapeutic applications.

Seaweeds are sources of bioactive compounds with medicinal properties, which make them attractive candidates for natural therapeutic agents. Marine brown algae are known to possess anti-inflammatory, hepatoprotective, anticancer properties, etc. Present study was carried out to identify the phytochemical constituents, antioxidant and cytotoxic activities of Sargassum prismaticum in two different solvents viz., chloroform and methanol. Chloroform was found to be the superior solvent for phenol and flavonoid extraction. Antioxidant activity was determined using DPPH and ABTS assays; however, the methanolic extract demonstrated better antioxidant potential. The highest cell cytotoxicity with an IC50 value of 7.6 ± 0.02 µg/mL was observed in methanolic extract, while the chloroform extract had an IC50 value of 9.6 ± 0.03 µg/mL against U937 cell line. These finding suggest that Sargassum prismaticum possesses potent antioxidant and cytotoxic properties, making it a potential candidate for further study as a novel antioxidant drug source.

Nyctanthes arbor-tristis alkaloids activates p53 independent cell death receptor and necroptosis pathways in HepG2 cells.

Nyctanthes arbor-tristis is a traditional medicinal plant with potential anti-cancer properties. In this study, crude and alkaloid extracts were prepared from different parts of the plant, and their cytotoxicity was evaluated on four different cancer cell lines. The alkaloid extracts from the leaf and fruit showed promising results, with the HepG2 cell line exhibiting significant cytotoxicity. The promising extracts were further studied for their apoptotic potential using various methods, including DNA fragmentation, TUNEL, Caspase-3 activity, Giemsa, and Hoechst staining. Our results indicated that the fruit extract had the highest apoptotic potential, with clear nuclear condensation, fragmentation, and apoptotic bodies observed. We also investigated the alteration of the Bax/Bcl-2 ratio both at the mRNA and protein levels. Our results showed a significant upregulation of the Bax gene and downregulation of the Bcl-2 gene for the fruit alkaloid extract. This indicates that the phenomenon of cell death expression might be following a p53-independent extrinsic pathway and Bax-activated caspase-independent AIF-mediated necroptosis in the HepG2 cancer cell line. Overall, our findings suggest that Nyctanthes arbor-tristis has potential as a therapeutic option for cancer treatment. The alkaloid extracts from the leaf and fruit may hold promise as a source of bioactive compounds for further development into anti-cancer agents. Further studies are needed to explore the underlying mechanisms of their cytotoxic and apoptotic effects and to evaluate their safety and efficacy in animal models and clinical trials.

Simultaneous use of high-volume Foley catheter (60 ml) and misoprostol for labor induction in nulliparous women: A randomized controlled trial.

OBJECTIVE: To examine the simultaneous effect of high-volume Foley catheter (HVFC) (60 ml) and vaginal misoprostol on labor induction in nulliparous women. METHODS: A randomized, double-blind, controlled trial was conducted among nulliparous post-date (>40 weeks) pregnant women between June and December 2019. At enrollment 100 women were randomized into each group (either HVFC and vaginal misoprostol or low-volume Foley catheter [LVFC] [30 ml] and vaginal misoprostol), for labor induction. Demographic and clinical data were collected at enrollment and delivery. RESULTS: Women in the HVFC group had statistically significantly shorter induction to delivery interval (median 860 min, interquartile range [IQR] 840-940 min vs. 1160 min, IQR 1080-1320 min, P < 0.001) and duration of labor (median 615 min, IQR 600-680 min vs. 750, IQR 692.5-800 min, P < 0.001). Mode of vaginal delivery (n = 94 vs. n = 78, P = 0.002), number of doses of misoprostol required (median 2, IQR 1-2 vs. 2, IQR 1-3), and need of oxytocin augmentation (n = 22 vs. n = 39, P = 0.014 and P < 0.001), was significantly better in the HVFC group. However, there was no significant difference with respect to other maternal or neonatal outcomes. CONCLUSION: Simultaneous use of HVFC and vaginal misoprostol for labor induction significantly shortens the induction to delivery interval and duration of labor in nulliparous women. TRIAL REGISTRATION: Clinical Trial Registry of India CTRI/2019/05/019394 (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=31554&EncHid=&userName=Foley%20catheter).

Identification of steroidal saponins from Tribulus terrestris and their in silico docking studies.

Tribulus terrestris is known to possess many pharmacological properties, most notably its anticancer activities, owing to its rich steroidal saponin contents. Even though many reports are available elucidating the anticancer potential of the herb, we, for the very first time have attempted to isolate and identified the active compound present in seed crude saponin extract and confers its in silico docking ability with various cellular targets proteins. High performance thin layer chromatography confirms the presence of active saponins in leaf and seed saponin extracts which were further fractionated by silica gel column chromatography. Fractions collected were assessed for cytotoxicity on human breast cancer cells. High resolution liquid chromatography and mass spectroscopy was employ to identify the active components present in fraction with highest cytotoxicity. Intriguingly, Nautigenin type of steriodal saponin was identified to present in the active fraction of seed extract (SF11) and the identified compound was further analyzed for its in silico docking interaction using PyRx AutodockVina. Docking studies revealed the high binding affinity of Nuatigenin at significant sites with apoptotic proteins Bcl-2, Bax, caspase-3, caspase-8, p53 and apoptosis inducing factor along with cell surface receptors estrogen receptor, projesterone receptor, epidermal growth factor receptor, and human epidermal growth factor receptor-2. Thus, the conclusions were drawn that saponin fraction of Tribulus terrestis possesses active compounds having anticancer property and specifically, Nuatigenin saponin can be considered as an important therapeutic drug for the breast cancer treatment.

An insight into the anticancer mechanism of Tribulus terrestris extracts on human breast cancer cells.

Tribulus terrestris (TT), a herb belonging to Zygophyllaceae family is widely used due to its medicinal properties. This study was undertaken to elucidate the anticancer mechanism of TT on MCF-7 breast cancer cells. Cytotoxic effect of the herb was assessed by 3-(4,5-diethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptotic potential was assessed through DNA fragmentation, TUNEL and caspase 3 activity assays. Expressions of genes regulating the apoptotic pathway were examined by RT-PCR and expression of proteins was analyzed by immunocytochemistry. The result of MTT assay revealed that methanolic and saponin extracts from leaves and seeds of TT were cytotoxic to MCF-7 cells. Cytotoxicity studies on peripheral blood mononuclear cells (PBMC) proved that TT extracts were non-toxic to non-malignant cells. Treatment of human breast cancer MCF-7 cells with seed and leaf methanol and saponin extracts of TT resulted in fragmentation of DNA and induction of apoptosis. This was evident by agarose gel electrophoresis of DNA and TUNNEL assay. The extracts of TT also caused a significant increase in caspase 3 activity in MCF-7 cells. TT extracts caused an induction of intrinsic apoptotic pathway which was evident by the upregulation in the expression of Bax and p53 genes and downregulation in the expression of Bcl-2. FADD, AIF and caspase 8 genes were also upregulated indicating the possible induction of extrinsic apoptotic pathway. Therefore, our results suggest that the Tribulus terrestris (TT) extracts may exert their anticancer activity by both extrinsic and intrinsic apoptotic pathways.

Effect of Tribulus terrestris saponins on proliferation of adipose-derived mesenchymal stem cells.

Adipose-derived mesenchymal stem cells (ASCs) transplantation has shown great promise for treating various diseases; however, poor viability of transplanted ASCs because of oxidative stress has limited its therapeutic efficiency. Plant saponins are recently been reported to have antioxidant activity tested in various cancer cell lines. This study was designed to investigate the protective effects of Tribulus terrestris saponins (TTS) on the proliferation of ASCs. The cytotoxic activity of hydrogen peroxide (H2 O2 ) was determined by treating ASCs with 100, 200, 300, 400, and 500 µM H2 O2 for 2 hours. ASCs were treated with 6.25, 12.5, 25, 50, and 100 µg/mL concentrations of TTS for the proliferative experiment. To check the protective effect of TTS, experiments were designed in two ways. In one set, ASCs were pretreated with different concentrations of TTS for 2 hours and then apoptosis was induced by treating them with 400 µM H2 O2 for next 2 hours, while in other set, ASCs were first treated with 400 µM H2 O2 for 2 hours and subsequently with different concentrations of TTS for 24 hours. The vitality and proliferation potential of cells were detected by 3-(4,5-Dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The result of the current study shows that in response to stress-induced by H2 O2 at concentration of 400 µM, ASCs underwent growth arrest and cell viability was reduced to half while treatment with TTS before and after H2 O2 exposure significantly prevents premature apoptosis. The findings suggest that saponins may act as an effective protective agent against oxidative stress-induced ASCs apoptosis.

Nonsteroidal estrogen receptor isoform-selective biphenyls.

Estrogen receptor (ER) has been a therapeutic target to treat ER-positive breast cancer, most notably by agents known as selective estrogen receptor modulators (SERMs). However, resistance and severe adverse effects of known drugs gave impetus to the search for newer agents with better therapeutic profile. ERα and ERß are two isoforms sharing 56% identity and having different physiological functions and expressions in various tissues. Only two residues differ in the active sites of the two isoforms motivating us to design isoform-selective ligands. Guided by computational docking and molecular dynamics simulations, we have designed, synthesized, and tested, substituted biphenyl-2,6-diethanones and their derivatives as potential agents targeting ERα. Four of the molecules synthesized exhibited preferential cytotoxicity in ERα+ cell line (MCF-7) compared to ERß+ cell line (MDA-MB-231). Molecular dynamics (MD) in combination with molecular mechanics-generalized Born surface area (MM-GBSA) methods could account for binding selectivity. Further cotreatment and E-screen studies with known ER ligands-estradiol (E2 ) and tamoxifen (Tam)-indicated isoform-selective anti-estrogenicity in ERα+ cell line which might be ER-mediated. ERα siRNA silencing experiments further confirmed the ER selective nature of ligands.

Mifepristone vs balloon catheter for labor induction in previous cesarean: a randomized controlled trial.

OBJECTIVE: To compare oral mifepristone (400 mg) with trans-cervical balloon catheter for induction of labor (IOL) in post date women with previous one cesarean section (CS). METHODS: In this randomized trial, post date pregnant women (gestation 40 weeks 5 days), with previous one low segment CS (no previous vaginal delivery) were induced either with oral mifepristone (400 mg) or balloon catheter [Foley's catheter (16 Fr); bulb filled with 30 ml normal saline]. They were re-assessed 24 and 48 h later. If at any time Bishop Score was >6; amniotomy was done, followed by oxytocin infusion. Primary outcome of the study was labor onset after first manoeuvre. Secondary outcomes were cervical ripening, need of oxytocin, vaginal delivery and CS, in two groups. RESULTS: From June 2012 to September 2015, we enrolled 107 women. Out of these, 57 received oral tablet mifepristone (400 mg) and 50 were inserted with balloon catheter. Labor onset after first manoeuvre was statistically significantly more in mifepristone group (37/57 vs. 13/50, respectively; p value 0.000). Bishop Score after 24 h was better in balloon catheter (p value 0.000). More women with balloon catheter required oxytocin for IOL (37/50 vs. 20/57, respectively; p value 0.000) along with higher dose [840 (320) mU vs 560 (120) mU, respectively, p value 0.000]. Failure of induction was statistically significantly higher in balloon catheter group (8 out of 50 vs. 2 out of 57, respectively, p value 0.043). There was no statistically significant difference in normal delivery or CS in either group (p value 0.242 and 0.331, respectively). CONCLUSION: Oral mifepristone (400 mg) is associated with statistically significantly higher incidence of labor onset in post date pregnant women with previous one CS, as compared to balloon catheter. Both methods are primarily for cervical ripening and oxytocin should not be delayed in the absence of onset of labor. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry-India, www.ctri.nic.in , CTRI/2012/05/003634.

A DNA intercalation methodology for an efficient prediction of ligand binding pose and energetics.

MOTIVATION: Drug intercalation is an important strategy for DNA inhibition which is often employed in cancer chemotherapy. Despite its high significance, the field is characterized by limited success in identification of novel intercalator molecules and lack of automated and dedicated drug-DNA intercalation methodology. RESULTS: We report here a novel intercalation methodology (christened ' Intercalate' ) for predicting both the structures and energetics of DNA-intercalator complexes, covering the processes of DNA unwinding and (non-covalent) binding. Given a DNA sequence and intercalation site information, Intercalate generates the 3D structure of DNA, creates the intercalation site, performs docking at the intercalation site and evaluates DNA-intercalator binding energy in an automated way. The structures and energetics of the DNA-intercalator complexes produced by Intercalate methodology are seen to be in good agreement with experiment. The dedicated attempt made in developing a drug-DNA intercalation methodology (compatible with its mechanism) with high accuracy should prove useful in the discovery of potential intercalators for their use as anticancers, antibacterials or antivirals. AVAILABILITY AND IMPLEMENTATION: http://www.scfbio-iitd.res.in/intercalate/. CONTACT: anjali@scfbio-iitd.res.in or bjayaram@chemistry.iitd.ac.in. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Gynecological diseases in rural India: A critical appraisal of indications and route of surgery along with histopathology correlation of 922 women undergoing major gynecological surgery.

OBJECTIVE: The aim of the study was to generate baseline data for indications of gynecological surgeries, and to assess route of surgery and histopathology correlation in women undergoing major gynecological surgery in a rural tertiary level teaching hospital in India. MATERIALS AND METHODS: Surgical indications, route of surgery and histopathology findings were reviewed and analyzed retrospectively, in 922 patients (≥35 years age) who underwent gynecological surgery at Dr. Rajendra Prasad Government Medical College, Kangra, Himachal Pradesh, India from January 1, 2011 to May 31, 2013. RESULTS: Of 922 surgeries, 65 had malignancy (7%). Pelvic organ prolapse (POP) (32.3%) and leiomyoma uterus (29%) were two most common benign indications for hysterectomy. Ovarian tumors were present in 13% (25% of these were malignant). Postmenopausal bleeding (PMB) was seen in 5.5% (55% of these were malignant). CONCLUSIONS: All except 10% surgeries were done in the absence of definite histopathology diagnosis that is dysfunctional uterine bleeding (n = 42 [45%]), chronic pelvic pain/severe dysmenorrhea (n = 34 [36%]) and recurrent PMB (n = 17 [19%]). Majority of surgeries had histopathological correlation except for six cases (0.6%) of malignancy, which were missed on initial work-up. Majority of the surgeries were done abdominally. In rural areas of developing countries poverty, lack of regular follow-up, resource constraints and lack of technical skills (with respect to laparoscopic/robotic surgeries) pose major challenge in providing quality health care.

A randomized controlled trial comparing cosmetic outcome after skin closure with 'staples' or 'subcuticular sutures' in emergency cesarean section.

OBJECTIVE: To compare staples with subcuticular sutures for skin closure in emergency Cesarean sections (CS). METHODS: One hundred and thirty women (undergoing emergency CS without previous abdominal delivery) were randomly assigned to either staples or subcuticular skin closure (monocryl 3-0). Primary outcome of the study was cosmetic outcome [as assessed by patient and independent observer: Patient Scar Assessment Scale (PSAS) and Observer Scar Assessment Scale (OSAS), respectively], 6 weeks post-operative. Secondary outcomes were wound complications, operating time, post-operative pain (visual analogue scale day 3 post-operative and patient assessment of pain in scar 6 weeks post-operative), and duration of hospital stay. RESULTS: 112 women were available for evaluation of scar 6 weeks post-operative. Cosmetic result of staples was significantly better than subcuticular sutures (PSAS and OSAS: p value 0.022 and 0.000, respectively), with significantly lesser duration of surgery (24 vs. 32 min: p value 0.000) and comparable post-operative pain (pain on day 3 and 6 weeks post-operatively: p value 0.474 and 0.179, respectively) and wound complications (p value 0.737). However, duration of stay in hospital was increased (6 vs. 3 days: p value 0.001). CONCLUSION: Staples are the method of choice for skin closure in emergency CS as they are significantly better than subcuticular sutures with respect to cosmesis and duration of surgery. Post-operative pain and wound complications are comparable in two groups. However, staples are associated with significantly increased duration of hospital stay. Trial registered in clinical trial registry CTRI: REF/2013/05/005087.

Angioleiomyoma uterus in an adolescent girl: a highly unusual presentation.

BACKGROUND: Uterine angioleiomyoma is a very rare gynecologic tumor; only a few such cases have been reported to date and we have found no such tumor reported in an adolescent girl. CASE: We report the case of a uterine angioleiomyoma in an adolescent girl. It presented as a huge abdomino-pelvic mass. The girl had severe menorrhagia and severe anemia. Intra-operatively no distinct planes were found between myoma and myometrium. Due to severe hemorrhage, she underwent sub-total abdominal hysterectomy. SUMMARY AND CONCLUSION: Uterine angioleiomyoma is an extremely rare tumor since only 16 such cases have been reported to date. Its appearance in an adolescent girl seems to be the first case of its kind. So it is being reported not only to familiarize the managing physicians with the possibility of such a tumor and its variable presentation, but also to highlight the need for inclusion of this tumor in WHO classification of tumors of the female genital tract.