Prognostic significance of programmed death-1 and programmed death ligand-1 proteins in breast cancer.

In numerous studies related to tumor prognosis, programmed death-ligand 1 (PD-L1) has been identified as a biomarker. This work aimed to determine the prognostic importance of PD-L1 in breast cancer. We searched electronic databases such as PubMed, Google scholar, home pages of publishing groups, medical, clinical, and pharmaceutical sciences journals, as well as other relevant sources to discover the importance of PD-1 and PD-L1 expression in breast cancer therapies and also recurrence. The keywords used in this search were autoimmunity, programmed cell death, PD-L1 or PD-1, and breast cancer. Our inclusion criteria included studies showing the synergy between the expression of PD-L1 and PD-1 in primary breast cancers as prognostic markers and this research was limited to humans only. We included review articles, original research, letters to the editor, case reports, and short communications in our study, published in English. We focused our work on PD-L1 mRNA expression in breast cancer cell lines. PD-L1 expression has been decisively demonstrated to be a high-risk factor for breast cancer with a bad prognosis.

Phytochemical Constituents and In vitro Pharmacological Response of Cnidium monnieri; A Natural Ancient Medicinal Herb.

Background: Natural medicines are being used for the treatment of various disorders due to pharmacological, therapeutical, and nutraceuticals characteristics. Objectives: Current research was planned to explore In vitro pharmacological response of phytochemical constituents extracted from C. monnieri' seeds using aqueous ethanol (70%). Methods: Qualitative and quantitative measurements for phytochemical constituents were performed following reference protocols. Then In vitro antioxidant potential, cytotoxic studies, antimicrobial, and spermicidal pharmacological response of C. monnieri extract were investigated. Results: The results of High Performance Liquid Chromatography (HPLC), Fourier Transform Infra-Red (FTIR) spectroscopy, and Atomic Absorption Spectrophotometer (AAS) explored the presence of wide range of bioactive compounds with significant (p<.05) antioxidant activities. Cytotoxic studies revealed significant (p<.05) protective behavior of C. monnieri evaluated using CtDNA damage protection, against Salmonella typhi TA98 and TA100, RBCs membrane stabilizing and clot lysis assay. It was also found that selected herb has antibacterial and antifungal activities. The results of spermicidal study on human (n = 30) spermatozoa revealed significant (p<.05) contraceptive per vaginal behavior of this natural medicinal plant. Conclusion: It could be concluded that C. monnieri showed significant pharmacological activities with non-toxic behavior, however In vivo study in animals and clinical trials are required to declare this natural herb as therapeutic agent.

Carrier-Free Cross-linked Laccase Crystals for Biocatalytic Degradation of Textile Industrial Effluents.

Herein, laccase from Trametes versicolor was used to fabricate carrier-free cross-linked laccase crystals (CLLCs) and deployed as a robust catalyst for waste effluent treatment. The surface morphology and involvement of functional group attributes of CLLCs were scrutinized by scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). As fabricated CLLCs were subjected to kinetic characterization by assessing the effects of pH environment, thermal profile, and substrate (determination of Km and Vmax) on the activity. A fully characterized CLLCs fraction was used to treat synthetic dyes containing waste effluents taken from various industries, i.e., Chenab Textile Industry, M-tax, Sitara, and National Silk & Rayon Mills. Degradation profile revealed 36.8%, 27.6%, 39.9%, and 26.4% degradation of Chenab Textile Industry, M-tax, Sitara, and National Silk & Rayon Mills, respectively, by the free form of laccase, whereas the biocatalytic activity of CCLCs led to 78.6%, 75.6%, 85.5%, and 63.3% degradation of those effluents. The decrease in peak and mass region alongside the presence of new peaks in GC-MS affirms the effective decolorization of contaminated waste effluents. CLLCs retained over 70% and 50% of their degradation activity after 3 and 5 cycles, respectively. In conclusion, CLLCs might represent a robust bioprocess to improve the usability of laccase for various synthetic dyes containing waste effluents to diminish environmental pollution from the dye-based industries.

Effects of methanolic and aqueous extracts of Ipomoea batatas L on mineral contents level (calcium and magnesium) in alloxan-induced diabetic rats.

In diabetic patients, electrolyte disorders frequently occur with the characteristic changes in minerals like calcium and magnesium etc. Several medicines are used to manage diabetes mellitus but they exert adverse effects. Plants are a valuable alternative to synthetic medicines because they are easily available, economical and have fewer side effects. Ipomoea batatas L is a well-known antidiabetic plant (sweet potato) but its effects on calcium and magnesium concentration have not studied. The prime focus of this study is to estimate the potential of Ipomoea batatas L peel-off on magnesium and calcium level in Alloxan-induced diabetic rats. Alloxan monohydrate was mixed in 0.9% NaCl solution and administrated [150 mg/kg (S/C)] to male Wistar rats to induce diabetes. After three days blood samples were collected and blood glucose level was recorded. Wistar rats having a blood glucose level of 200 mg/dl and above were selected for the study. Methanol and water extract of Ipomoea batatas L peel-off was given orally with a dose rate of 4g/day. Calcium and magnesium estimation was done using an atomic absorption spectrophotometer. Our results revealed an increase in both the calcium and magnesium level in heart, brain, liver, hind limb, and forelimb after Ipomoea batatas extract treatment. In kidneys decreased calcium level was noted as they excrete calcium. Mineral (Calcium, magnesium) level was increased in all organs except kidney after both extracts treatment. Ipomoea batatas being anti-diabetic in nature also maintain the homeostasis of calcium and magnesium in diabetes. Therefore, we propose the long-term use of such agents might help in the prevention of diabetes-associated complications. However, the validation of these results to human population needs further extensive study.

Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus: A systematic review.

Viral infections are being managed therapeutically through available antiviral regimens with unsatisfactory clinical outcomes. The refractory viral infections resistant to available antiviral drugs are alarming threats and a serious health concern. For viral hepatitis, the interferon and vaccine therapies solely are not ultimate solutions due to recurrence of hepatitis C virus. Owing to the growing incidences of viral infections and especially of resistant viral strains, the available therapeutic modalities need to be improved, complemented with the discovery of novel antiviral agents to combat refractory viral infections. It is widely accepted that medicinal plant heritage is nature gifted, precious, and fueled with the valuable resources for treatment of metabolic and infectious disorders. The aims of this review are to assemble the facts and to conclude the therapeutic potential of medicinal plants in the eradication and management of various viral diseases such as influenza, human immunodeficiency virus (HIV), herpes simplex virus (HSV), hepatitis, and coxsackievirus infections, which have been proven in diverse clinical studies. The articles, published in the English language since 1982 to 2017, were included from Web of Science, Cochrane Library, AMED, CISCOM, EMBASE, MEDLINE, Scopus, and PubMed by using relevant keywords including plants possessing antiviral activity, the antiviral effects of plants, and plants used in viral disorders. The scientific literature mainly focusing on plant extracts and herbal products with therapeutic efficacies against experimental models of influenza, HIV, HSV, hepatitis, and coxsackievirus were included in the study. Pure compounds possessing antiviral activity were excluded, and plants possessing activity against viruses other than viruses in inclusion criteria were excluded. Hundreds of plant extracts with antiviral effect were recognized. However, the data from only 36 families investigated through in vitro and in vivo studies met the inclusion criteria of this review. The inferences from scientific literature review, focusing on potential therapeutic consequences of medicinal plants on experimental models of HIV, HSV, influenza, hepatitis, and coxsackievirus have ascertained the curative antiviral potential of plants. Fifty-four medicinal plants belonging to 36 different families having antiviral potential were documented. Out of 54 plants, 27 individually belong to particular plant families. On the basis of the work of several independent research groups, the therapeutic potential of medicinal plants against listed common viral diseases in the region has been proclaimed. In this context, the herbal formulations as alternative medicine may contribute to the eradication of complicated viral infection significantly. The current review consolidates the data of the various medicinal plants, those are Sambucus nigra, Caesalpinia pulcherrima, and Hypericum connatum, holding promising specific antiviral activities scientifically proven through studies on experimental animal models. Consequently, the original research addressing the development of novel nutraceuticals based on listed medicinal plants is highly recommended for the management of viral disorders.

Effect of UDP-Glucuronosyltransferase (UGT) 1A Polymorphism (rs8330 and rs10929303) on Glucuronidation Status of Acetaminophen.

Interindividual variability in polymorphic uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) ascribed to genetic diversity is associated with relative glucuronidation level among individuals. The present research was aimed to study the effect of 2 important single nucleotide polymorphisms (SNPs; rs8330 and rs10929303) of UGT1A1 gene on glucuronidation status of acetaminophen in healthy volunteers (n = 109). Among enrolled volunteers, 54.13% were male (n = 59) and 45.87% were female (n = 50). The in vivo activity of UGT1A1 was investigated by high-performance liquid chromatography-based analysis of glucuronidation status (ie, acetaminophen and acetaminophen glucuronide) in human volunteers after oral intake of a single dose (1000 mg) of acetaminophen. The TaqMan SNP genotyping assay was used for UGT1A1 genotyping. The wild-type genotype (C/C) was observed the most frequent one for both SNPs (rs8330 and rs10929303) and associated with fast glucuronidator phenotypes. The distribution of variant genotype (G/G) for SNP rs8330 was observed in 5% of male and 8% of the female population; however, for SNP rs10929303, the G/G genotype was found in 8% of both genders. A trimodal distribution (fast, intermediate, and slow) based on phenotypes was observed. Among the male participants, the glucuronidation phenotypes were observed as 7% slow, 37% intermediate, and 56% fast glucuronidators; however, these findings for the females were slightly different as 8%, 32%, and 60% respectively. The k-statistics revealed a compelling evidence for good concordance between phenotype and genotype with a k value of 1.00 for SNP rs8330 and 0.966 for SNP rs10929303 in our population.

Age-Dependent Hepatic UDP-Glucuronosyltransferase Gene Expression and Activity in Children.

UDP-glucuronosyltransferases (UGTs) are important phase II drug metabolism enzymes. The aim of this study was to explore the relationship between age and changes in mRNA expression and activity of major human hepatic UGTs, as well as to understand the potential regulatory mechanism underlying this relationship. Using previously generated data, we investigated age-dependent mRNA expression levels of 11 hepatic UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B10, UGT2B15, and UGT2B17) and 16 transcription factors (AHR, AR, CAR, ESR2, FXR, GCCR, HNF1a, HNF3a, HNF3b, HNF4a, PPARA, PPARG, PPARGC, PXR, SP1, and STAT3) in liver tissue of donors (n = 38) ranging from 0 to 25 years of age. We also examined the correlation between age and microsomal activities using 14 known UGT drug substrates in the liver samples (n = 19) of children donors. We found a statistically significant increase (nominal p < 0.05) in the expression of UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT2B7, and UGT2B17, as well as glucuronidation activities of serotonin, testosterone, and vorinostat during the first 25 years of life. Expression of estrogen receptor 1 and pregnane X receptor, two strong UGT transcriptional regulators, were significantly correlated with both age and UGT mRNA expression (p ≤ 0.05). These results suggest that both UGT expression and activity increase during childhood and adolescence, possibly driven in part by hormonal signaling. Our findings may help explain inter-patient variability in response to medications among children.

Genetic polymorphism of UDP-glucuronosyltransferase (UGT2B15) and glucuronidation of paracetamol in healthy population.

Inter individual variability in polymorphic UDP-glucuronosyltransferase (UGT2B15) has been associated with varied glucuronidation level. The present project was designed to determine the genetic polymorphism of UDP-glucuronosyltransferase (UGT2B15) and glucuronidation of paracetamol in healthy (male=59 and female=50) population. The association between genotype (UGT2B15) and phenotype (paracetamol glucuronidation) has been evaluated. According to trimodal model, genotypes and phenotypes were categorized as fast, intermediate and slow glucuronidators. Presence of wild type allele illustrated a UGT2B15 genotype as fast glucuronidator. The glucuronidation status was investigated by HPLC analysis of paracetamol. Ratio of paracetamol glucuronide to paracetamol was determined with two antimodes at glucuronidation ratio of 0.3 and 1.8. In our study, 7% and 12% of population was distributed as slow glucuronidators by phenotype and genotype, respectively and association between phenotype and genotype was good for analysis of glucuronidation status as displayed by kappa value (0.792).