BackgroundCervical squamous cell carcinoma (CSCC) is a major cause of female mortality worldwide. This study has examined epidermal growth factor receptor (EGFR) pathway markers that represent actionable pharmacological targets.MethodsHPV16 positive CSCCs (n = 105 patients) from Madhya Pradesh, India were screened for KRAS and PIK3CA mutations by PNA-clamp real-time PCR. Immunohistochemistry (IHC) was performed for EGFR, PIK3CA, PTEN, phospho-AKT, phospho-mTOR and phospho-44/42 MAPK (ERK1/2).ResultsKRAS mutations were detected in 0/91 (0%) and PIK3CA mutations in 19/95 (20.0%) informative specimens: exon 9, E542 (n = 3) and E545 (n = 15); exon 20, H1047R (n = 1). PIK3CA mutation detection was associated with older mean patient age [48.2 vs. 56.6 years (P = 0.007)] and with post-menopausal age: 5/45 (11.1%) patients <50 years vs. 14/50 (28.0%) patients ≥50 years (P = 0.045; OR = 3.11). EGFR expression was present in 60/101 (59.4%) CSCCs and was associated with PIK3CA mutation detection (P < 0.05) but not age (P > 0.05). EGFR and phospho-AKT staining showed associations with tumor grade and/or lymph node status (P < 0.05). Significant associations were not found for the other study markers (P > 0.05).ConclusionThese data show that PIK3CA mutation acquisition is related to patient age and EGFR expression. The absence of KRAS mutations supports the potential of anti-EGFR therapies for CSCC treatment. The relatively high PIK3CA mutation rates indicate that PI3K may be a therapeutic target for a significant subset of CSCC patients. Qualitatively distinct IHC staining profiles for the marker panel were noted patient to patient; however, across patients, consistent linear relationships between up- and downstream pathway markers were not observed. Evaluation of the expression status of potential cancer pathway targets may be of value in addition to molecular profiling for choosing among therapeutic options.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0611-0) contains supplementary material, which is available to authorized users.

The results clearly indicate toward the memory-enhancing effect of LCZE, which could be due to the synergistic effect of anti-AChE and antioxidant activities.

In the current study, anovulatory endometrium and luteal phase defect are the major causes of infertility, and tuberculous endometritis, non-specific endometritis and GSD are minor contributing factors. These are treatable causes. Premenstrual endometrial biopsy, if accompanied by information of menstrual cycle and date of biopsy, can be a very reliable diagnostic tool for hormonal dysfunction and intrinsic endometrial factors in infertility.

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Invasive cervical carcinoma (ICC) remains a leading cause of female mortality in India. There is a paucity of data about human papillomavirus (HPV) type distribution among ICCs from Central India. Formalin-fixed, paraffin-embedded ICC specimens (n=270 patients) from Madhya Pradesh state were screened for HPV by GP5/6 primer-based polymerase chain reaction followed by cycle sequencing and NCBI BLAST search. HPV was detected in 93.3% of the tumors. Thirteen types were detected: HPV16 (73.7%), HPV18 (11.9%), HPV45 (2.2%), HPV66 (1.5%), HPV35 (1.1%), and HPV56 (0.7%). HPV31, 51, 58, 59, 67, 82 and JEB2 were each seen in 1 case (0.4%). HPV16 was more common among women less than 40 yr than 40 yr or older (P=0.006), and HPV18 was more common in women aged 40 yr or older (P=0.013). Squamous cell carcinomas were more frequently HPV-positive than adenocarcinomas (P=0.01). HPV18 was more common in adenocarcinoma than in squamous cell carcinoma (P=0.02). These data contribute to the pan-India profile of HPV-type relationship to ICC and show the potential of current vaccines to greatly relieve (by up to 85.6%) the ICC burden in Central India. The findings are also suggestive that next-generation HPV vaccines might be designed on a regional basis rather than from compounded global data.

Background Curcumin, a natural polyphenol from Curcuma longa, is known to possess diversified pharmacological roles including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic properties; however, its bioavailability is severely limited due to its poor solubility, poor absorption, rapid metabolism, and significant elimination. Hydrazinocurcumin (HZC), a novel analogue of curcumin has been reported to overcome the limitations of curcumin and also possesses multiple pharmacological activities. The present study aimed to evaluate the unexplored pharmacokinetic profile of this agent in experimental rats. Methods Drug formulations were administered to the experimental animals via oral, intravenous and intraperitoneal routes. Blood samples were collected at different pre-determined time intervals to determine the pharmacokinetic parameters. To understand the biodistribution profile of HCZ, tissue samples were isolated from different groups of Sprague-Dawley rats at different time points. The pharmacokinetic parameters of HZC were evaluated after administration through oral (100 mg/ kg), intraperitoneal (100 mg/kg) and intravenous (10 mg/kg) routes. Results Significantly (p < 0.05) higher total AUC along with maximum concentration were evident with intraperitoneal administration when compared to the results of oral administration at a similar dose. In addition, shorter time to peak was observed with intraperitoneal administration. These results revealed a faster rate and longer duration of absorption with intraperitoneal administration, which further resulted in enhanced absolute bioavailability of HZC (29.17%) when compared to 5.1% upon oral dosing. The obtained data from the pharmacokinetic study indicated that HZC was instantaneously distributed and moderately eliminated from body fluids. Conclusion Based on the findings, it could be concluded that absorption of HZC is much higher via intraperitoneal route of administration compared to the oral administration.

Coronavirus Disease-2019 (COVID-19) is a highly contagious disease caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) classified the disease a as global public health hazard on 11 March 2020. Currently, there are no adequate measures to combat viral infections, including COVID-19, and the medication guidelines for the management of COVID-19 are dependent on previous findings from SARS-CoV and MERS-CoV research. Natural products have achieved widespread acceptance around the world as a means of enhancing healthcare and disease prevention. Plants are a potential source of antiviral factors such as flavonoids, phenolic acids, terpenoids, and others. Some of these agents exhibit a broad spectrum of antiviral activity. This study aimed to screen herbal leads for possible inhibitors of the SARS-CoV-2 ADP Ribose Phosphatase enzyme (ARP). Guggulsterone was found to be highly stabilized within the active site of the viral ARP enzyme by molecular dynamic simulation with very little fluctuation throughout the simulation timeframe of 100 ns. Thus, guggulsterone can be further used to develop a safe and competent medication for evolving therapy against SARS-CoV-2 in post-preclinical and clinical trials.

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