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الملخص: أهداف البحث: يهدف هذا البحث إلى تقييم الآثار قبل السريرية المضادة للسرطان للميتفورمين في نموذج طُعم أجنبي لسرطان الثدي. طرق البحث: أجريت هذه التجربة التداخلية خلال فترة محددة مدتها خمسة أشهر (أغسطس ٢٠١٦ - يناير ٢٠١٧). حيث استخدمنا نموذج طُعم أجنبي من الفئران بلب/ج عارية. وكان حجم العينة ٥٠ فأرا، وُزعت لمجموعتين المجموعة أ والمجموعة ب لمجموعتي الميتفورمين والتحكم السلبية، على التوالي. وتم تقييم النشاط السرطاني للميتفورمين من خلال مقارنة حجم الورم، ووزن الورم، ونسبة تراجع الورم، ونسبة التراجع المئوية ومعدل البقاء على قيد الحياة. النتائج: بالمقارنة مع مجموعة التحكم، خفض الميتفورمين بشكل كبير تطور الورم في نموذج الطُعم الأجنبي لسرطان الثدي الناجم حسب مؤسسة ميتشغان للسرطان-٧. وقد انعكس ذلك من خلال اختلافات كبيرة في حجم الورم في المتابعة النهائية. وقد تم دعم النتائج التي توصلنا إليها من خلال انخفاض كبير في معدل نمو الورم ووزن الورم في مجموعة الميتفورمين مقارنة بمجموعة التحكم. وبالمثل، كان معدل البقاء الكلي وتراجع الورم مرتبطين بشكل أكبر في مجموعة الميتفورمين. الاستنتاجات: أثبتت هذه الدراسة أن الميتفورمين يمكن أن يقلل بشكل كبير من نمو الورم ويمكن أن يزيد من معدل البقاء على قيد الحياة في نموذج الطُعم الأجنبي لسرطان الثدي. Abstract: Objective: This research aims to evaluate the preclinical meritorious and anticancer effects of Metformin in a Xenograft model of breast cancer. Methods: This interventional trial was conducted during a defined period of 5 months (August 2016 January 2017). We used a Xenograft model of nude BALB/c mice. A sample size of 50 mice, allocated into two groups and designated as Group A and Group B for Metformin and negative control groups, respectively. The anticancer activity of Metformin has been evaluated by comparing the tumour volume, tumour weight, tumour regression ratio, percentage regression, and survival rate. Results: Compared with the control group, Metformin can significantly reduce the progression of tumour in the Xenograft model of breast cancer induced by MCF-7. This is reflected by significant differences in tumour volume at the final follow-up (p =

Heavy metal pollution is a great hazard to the environment that enters the ecosystem through different natural and anthropogenic sources. A study was performed to evaluate concentrations of Cd and Pb in selected plants, Ricinus communis and Parthenium hysterophorus, and soils from different functional sites in Sialkot. Maximum fresh and dry weights of R. communis were recorded from control and field sites. Highest concentrations of Cd in P. hysterophorus (33.5 mg kg−1) and R. communis (24.36 ± 2.83 mg kg−1) were recorded at residential and industrial sites, respectively. However, road site samples showed maximum concentrations of Pb both in R. communis (9.06 ± 0.35 mg kg−1) and P. hysterophorus (7.90 ± 0.36 mg kg−1). Soil from the road site were found to be highly acidic (pH 4.75 ± 0.04), while the field site showed highest EC (494 ± 3.60) and TDS (509 ± 3.00) values. Generally, there were reductions in chlorophyll a and carotenoids, but an increase in chlorophyll b was observed in both plants at all sites compared to the control.

Cells are exposed to several environmental or chemical stressors that may cause DNA damage. DNA damage alters the normal functioning of the cell and contributes to several diseases, including cancer. Cells either induce DNA damage repair pathways or programmed cell death pathways to prevent disease formation depending on the severity of the stress and the damage caused. The DNA repair mechanisms are crucial to maintaining genome stability. During this adaptive response, the heat shock proteins (HSPs) are the key players. HSPs are overexpressed during genotoxic stress, but the role of different molecular players in the interaction between HSPs and DNA repair proteins is still poorly understood. As DNA damage promotes genomic instability and proteotoxic stress, modulating the protein quality control systems like the HSPs network could be a promising strategy for targeting disease pathologies associated with genomic instability, such as cancer. Hence, this review highlights the role of HSPs in DNA repair pathways. Further, the review also provides an outlook on the role of genomic instability and protein homeostasis in cancer, which is crucial to understanding the mechanisms behind its survival and developing novel targeted therapies.

Objectives In preterm infants, hyperbilirubinemia is common and can impair the central nervous system. The tests available for measuring bilirubin is to collect blood from heel pricking and occasionally taking blood samples from inserted cannulas, which is painful. Therefore, there is a need to develop a non-invasive device to detect bilirubin levels in newborns and interpret the severity of jaundice. Methods We conducted a cross-sectional study of 100 neonates. Patient data was collected between June 2015 and December 2016 from King Khalid Hospital at Al-Majma'ah, Saudi Arabia, and Alpine Hospital, Gurgaon, India. The mean gestational age of neonates was 39.0 weeks. Total bilirubin was measured using a transcutaneous bilirubinometer on the forehead and obtaining optical imaging through scanning of conjunctiva of eyes, also referred to as BiliChek and BiliCapture, respectively. Later the blood samples were obtained from these patients and tested in the laboratory to determine total serum bilirubin (TSB) levels. Results The concentration of bilirubin as measured from serum, BiliChek, and BiliCapture were 10.7±2.0, 11.6±2.7, and 13.1±2.3 mg/dL, respectively. Correlation was high between TSB and BiliChek (r2 = 0.88) and between TSB and BiliCapture (r2 = 0.73). The Bland-Altman plots showed good agreement when comparing bilirubin values for both BiliChek and BiliCapture devices. Bilirubin measurement was further checked for the sensitivity and specificity and was 88.0% and 76.0% using BiliChek and 92.0% and 75.6% using BiliCapture, respectively. Conclusions The optical imaging of conjunctiva for bilirubin assay is a safe alternative to a laboratory bilirubin assay and transcutaneous bilirubinometer BiliChek.

Many leather processing industries in Sialkot, Pakistan, discharge their wastes freely into the environment which then enters nearby water bodies. Irrigation practices with these polluted waters pose a great threat to the soil quality. Hence, the soils and effluent waters of five famous leather processing sites were evaluated for the presence of As, Cr, Cd, Ni, Zn, Mn, Mg, Na, K, and Ca. High mean concentrations of As (112.6 mg kg−1), Cr (45.9 mg kg−1), Cd (2.0 mg kg−1), Ni (58.2 mg kg−1), Zn (117.6 mg kg−1), Mn (12.8 mg kg−1), Mg (34,511 mg kg−1), Na (16,292 mg kg−1), K (1765 mg kg−1), and Ca (4387 mg kg−1) were found in soils at our study sites. Effluents were found to be highly acidic with high TDS content and high EC values. Index of Geoaccumulation (Igeo) confirmed the extremely toxic nature of these soils. Plants growing at these sites also showed high concentrations of As, Cr, and Cd in their leaves.

Cilia both receive and send information, the latter in the form of extracellular vesicles (EVs). EVs are nano-communication devices that influence cell, tissue, and organism behavior. Mechanisms driving ciliary EV biogenesis are almost entirely unknown. Here, we show that the ciliary G-protein Rab28, associated with human autosomal recessive cone-rod dystrophy, negatively regulates EV levels in the sensory organs of Caenorhabditis elegans in a cilia specific manner. Sequential targeting of lipidated Rab28 to periciliary and ciliary membranes is highly dependent on the BBSome and the prenyl-binding protein phosphodiesterase 6 subunit delta (PDE6D), respectively, and BBSome loss causes excessive and ectopic EV production. We also find that EV defective mutants display abnormalities in sensory compartment morphogenesis. Together, these findings reveal that Rab28 and the BBSome are key in vivo regulators of EV production at the periciliary membrane and suggest that EVs may mediate signaling between cilia and glia to shape sensory organ compartments. Our data also suggest that defects in the biogenesis of cilia-related EVs may contribute to human ciliopathies.

Objectives To evaluate the effect of Atorvastatin as an adjuvant with betamethasone valerate on disease severity and cardiovascular risks in chronic plaque type psoriatic patients. Methods It is an interventional study conducted in Pharmacology Department of BMSI, JPMC with the collaboration of Dermatology Department of JPMC, Karachi. The duration of study was from June 2013 to June 2016. Seventy five psoriatic patients were prescribed Tablet Atorvastatin 40-20 mg/day (40mg for first three months twice daily followed by 20mg once daily for the next three month) plus topical Betamethasone Valerate 0.1% once daily for 6 months (three week apply than one week interval). The efficacy and safety profile of drugs was measured by PASI, DLQI, hsCRP, LFTS and Lipid profile. Results The percentage change of PASI is 86.749±0.547, DLQI is 82.697±.2.61 and hsCRP is 40.371±8.505, which showed highly significant improvement in patient at the end of last follow up. LFTs and CPK for safety profile of therapy showed non-significant results. Conclusion Atorvastatin used as an adjuvant therapy with currently existing standard therapy (topical betamethasone) in patients having mild to moderate plaque type psoriasis reduces disease severity and cardiovascular risks.

This article looks into the instances of growing waterlogging, which is a negative externality of the developmental process (canal irrigation) that has affected the marginalised sections to a greater extent, who mostly depend on land for livelihood and self-sustenance. Land-use pattern has undergone a tremendous transformation due to irrigation development in terms of increase in fallow and culturable waste lands. Fertility of the land has considerably been reduced: agricultural production has gone down, animals and trees have been diminished, livelihood and employment opportunities have declined, largely affecting the Other Backward Castes and Scheduled Castes living in its lower catchments that have sub-marginal landholdings and are historically marginalised, thus leading to higher incidence of migration among the local inhabitants of the basin. The study recommends how integrated land and water development programmes at village level could improve land utilisation pattern. These changes would indirectly increase agricultural productivity, enhance livelihood of the farmers and the local communities by increasing employment and livelihood activities at village level. The employment scheme National Rural Employment Guarantee Scheme (NREGS) would be of crucial importance in managing water resources and enhancing land development simultaneously.

In recent years, customer satisfaction has been a subject of great interest in order to maximize the profit levels of the organizations. The quality of service provided by the organizations has become an important aspect of customer satisfaction. It has been a universal fact that service quality is proportionally related to customer satisfaction. It is obvious that customers play an important role in the organizational process (Lee & Ritzman, 2005, p. 92). Building customer relationship means delivering superior value over competitors to the target customers (Kotler et al., 2002, p. 391). Many companies are adopting quality management programs which aim at improving the quality of their products and marketing processes, because it has been proven that “quality has a direct impact on product performance, and thus on customer satisfaction” (Kotler et al., 2002, p. 8).The primary objective of this study is to examine the relationship between customer satisfaction and service quality in retail sectors with respect to the service quality dimensions with special reference to the hypermarkets in the Kingdom of Saudi Arabia (KSA).

NF-E2 p45-related factor 2 (Nrf2) is a cap 'n' collar (CNC) basic region-leucine zipper (bZIP) transcription factor that imparts cellular defence against xenobiotic and oxidative stress evoked responses by inducing an array of cytoprotective genes. Essential factors that regulate Nrf2 activity and stability during analgesic nephropathy are incompletely understood. In this study, we demonstrate that acetaminophen (a classic analgesic) posit nephrotoxicity both in vitro and in vivo via PHLPP2 activation. Enhanced PHLPP2 levels down regulate p-Akt by dephosphorylating it at Ser 473 residue leading to Gsk3β activation. APAP subsided Nrf2 nuclear accumulation by activating Gsk3β which phosphorylates Fyn kinase. p-Fyn kinase translocates into the nucleus and phosphorylates Nrf2 (Tyr 568) leading to its nuclear export, ubiquitination and degradation. Therefore, poor prognosis prevails during analgesic nephrotoxicity because of the defects in Akt-1/Gsk3β/Fyn-Nrf2 signaling pathway. Morin, a bioflavonoid given as co- and pre-treatment with acetaminophen significantly prevented the toxicity induced damage by constitutively stabilizing Nrf2 nuclear retention. Diminished Nrf2 levels by APAP overdose imposed severe proximal tubular damage leading to apoptotic cell death. Morin, as a potent Nrf2 inducer accorded protection against acetaminophen induced renal damages by its molecular intervention with Akt-1/Gsk3β/Fyn kinase pathway via PHLPP2 de-activation.

Transfusion transmitted infections are major problem associated with blood transfusion. Accurate estimates of risk of TTIs are essential for monitoring the safety of blood supply and evaluating the efficacy of currently employed screening procedures. The present study was carried out to assess the percentage of voluntary donors and replacement donors and to find out prevalence and changing trends of various TTIs blood donors in recent years. A study was carried out on blood units of voluntary and replacement donors which were collected from January 2008 to December 2012. On screening of 180,371 replacement units, seropositivity of transfusion transmitted disease in replacement donors was 0.15% in HIV, 1.67% in hepatitis B surface antigen, 0.49% in hepatitis C virus, 0.01% in VDRL, and 0.009% in malaria. Of 11,977 voluntary units, seropositivity of transfusion transmitted disease in voluntary donors was 0.08% in HIV, 0.24% in hepatitis B surface antigen, 0.001% in hepatitis C virus, 0.008% in VDRL (sexually transmitted disease), and 0.01% in malaria. From results it has been concluded that prevalence of transfusion transmitted infection (HIV, HBV, HCV, VDRL, and malaria) was more in replacement donors in comparison to voluntary donors. Extensive donor selection and screening procedures will help in improving the blood safety.