The present study compares the in vitro effects of nanoparticles loaded pentamidine drug and conventional pentamidine on Leishmania tropica. Herein, pentamidine-loaded chitosan nanoparticles (PTN-CNPs) have been synthesized through an ionic gelation method with sodium tripolyphosphate (TPP). Next, the physical characteristics of PTN-CNPs were determined through the surface texture, zeta potential, in vitro drug release, drug loading content (DLC), and encapsulation efficacy (EE) and compared its efficacy with free pentamidine (PTN) drug against promastigotes and axenic amastigotes forms of L. tropica in vitro. The PTN-CNPs displayed a spherical shape having a size of 88 nm, an almost negative surface charge (-3.09 mV), EE for PTN entrapment of 86%, and in vitro drug release of 92% after 36 h. In vitro antileishmanial activity of PTN-CNPs and free PTN was performed against Leishmania tropica KWH23 promastigote and axenic amastigote using 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyletetrazolium bromide (MTT) assay. It was observed that the effect of PTN-CNPs and free PTN on both forms of the parasite was dose and time dependent. Free PTN presented low efficacy even at higher dose (40 µg/ml) with 25.6 ± 1.3 and 26.5 ±1.4 mean viability rate of the promastigotes and axenic amastigotes, respectively after 72 hrs incubation. While PTN-CNPs showed strong antileishmanial effects on both forms of parasite with 16 ± 0.4 and 19 ± 0.7 mean viability rate at the same higher concentration (40 µg/ml) after 72 hrs incubation. Half maximal inhibitory concentration (IC50) values of PTN-CNPs toward promastigotes and amastigotes were obtained as 0.1375 µg/ml and 0.1910 µg/ml, respectively. In conclusion, PTN-CNPs effectively inhibited both forms of the L. tropica; however, its effect was more salient on promastigotes. This data indicates that the PTN-CNPs act as a target drug delivery system. However, further research is needed to support its efficacy in animal and human CL.

Objective: To evaluate the antiviral activity and phytochemicals of selected plant extracts and their effect on the mitogen-activated protein kinase (MAPK) signaling pathway modulated by hepatitis C virus (HCV) nonstructural protein 5A (NS5A). Methods: A total of ten plant extracts were initially screened for their toxicities against HepG2 cells. The non-toxic plants were tested for their inhibitory effect on the expression of HCV NS5A at both mRNA and protein levels using real-time PCR and Western blotting assays, respectively. The differential expression of the genes associated with MAPK pathway in the presence of NS5A gene and plant extract was measured through real-time PCR. Subsequently, the identification of secondary metabolites was carried out by phytochemical and HPLC analysis. Results: The phytochemical profiling of Berberis lyceum revealed the presence of alkaloids, phenols, saponins, tannins, flavonoids, carbohydrates, terpenoids, steroids, and glycosides. Similarly, quercetin, myricetin, gallic acid, caffeic acid, and ferulic acid were identified through HPLC analysis. The methanolic extract of Berberis lyceum strongly inhibited HCV RNA replication with an IC50 of 11.44 μg/mL. RT-PCR and Western blotting assays showed that the extract reduced the expression of HCV NS5A in a dosedependent manner. Berberis lyceum extract also attenuated NS5Ainduced dysregulation of the MAPK signaling pathway. Conclusions: Our findings suggest that Berberis lyceum extract strongly inhibits HCV propagation by reducing HCV NS5Ainduced perturbation of MAPK signaling.

Bacterial mediated Silver nanoparticles is considered as an emerging Ecofriendly approach to eradicate human pathogens. This paper aims to provide the biological approach for the synthesis of silver nanoparticles from indigenously isolated bacteria. This study will be beneficial to control the nosocomial infections triggered by MRSA (Methicillin-resistant Staphylococcus aureus). The current study is the extracellular synthesis of silver nanoparticles by using the cell free filtrate of bacterial strains isolated from the soil. The optimization study was also carried out to obtain the maximum production of silver nanoparticles. Nanoparticles were confirmed and characterized by UV-Vis spectroscopy and Transmission Electron Microscopy (TEM) having the plasmon resonance peak between 420-450nm with 10-60nm in size range and most were spherical in shape. Synthesized silver nanoparticles showed a potential antibacterial activity against MRSA (Methicillin Resistant Staphylococcus aureus) in-vitro study. This is the green approach for the production of AgNPs, as there was no previous work done on the synthesis of silver nanoparticles by bacteria in this region of Southern Punjab, Pakistan and these nanoparticles can be used to treat nosocomial infection. These silver nanoparticles can be used in effective disease management as antimicrobial agent.

Objective: To explore antioxidant potential, anti-cancer activity, and phytochemicals of Commelina benghalensis L. Methods: The roots of Commelina benghalensis were extracted in different solvents (methanol, ethanol, benzene, chloroform, n-hexane) with a range of polarity. Antioxidant activity was evaluated by reducing power assay, DPPH radical scavenging activity and phosphomolybdenum method, cytotoxicity by MTT assay, apoptotic and cell cycle analysis by flow cytometry, migratory and invasive potential by wound scratch assay and invasion assay, respectively, functional groups analysis by FT-IR spectroscopy and phytochemicals by aluminum chloride colorimetric and Folin-Ciocalteu methods. Results: The extracts showed worthy antioxidant potential. The chloroform extract demonstrated the most significant cytotoxic effect on MDA-MB-231 (breast cancer) cell line, induced apoptosis and reduced migratory and invasive potential of MDA-MB-231 cells. Methanol and ethanol extracts presented good yield of total phenolic and total flavonoid contents. The FTIR spectroscopic studies revealed different characteristic peak values with various functional compounds such as alkenes, alkanes, aliphatic amines, aromatics, alkyl halides, carboxylic acid, alcohols, ester, aldehydes and ketones. Conclusions: The results demonstrate the potential use of Commelina benghalensis as a good antioxidant with significant anti-cancer effect.

No abstract available.
Humans ; Ichthyosis ; Ichthyosis, Lamellar

Breast cancer is a frightful disease and serious concern in women around the world causing significant health care burden in both developed and developing countries. Extensive research work has shown that breast cancer provides strong resistance to chemical agents, UV radiation, and hormonal treatments. It is generally accepted that cell genetics is not the only main reason for breast cancer and genetic risk factors, for example, mutations in BRCA1 and BRCA2 genes constitute 5%-10% of all breast cancer rates. Other related factors include age, gender, race, ethnicity, weight, reproductive factors, exo- and endogenous hormonal exposures, oral contraceptives use, ultraviolet radiation, diet, and night work (circadian disruption). Many studies have revealed that dietary isoflavones regulate breast cancer occurrence, recurrence and prognosis. Dietary isoflavones have long been part of Asian population diet and there is a significant increase as compared to dietary isoflavones intake among other populations. Dietary isoflavones are natural phytoestrogens having both estrogenic and anti-estrogenic potentials on breast cancer cells in culture, animal models and in experimental trials. This literature survey provides a comprehensive overview on the tumor preventive and tumor promoting potentials of dietary isoflavones on breast cancer. In addition, this paper provides a literature review of dietary isoflavones and their effects on up-regulation and down-regulation of different signaling pathways, genes and proteins. Finally, future perspectives of dietary isoflavones and breast cancer researchers are also critically discussed, which will provide a deeper insight regarding the inner molecular mechanisms of action.

The National Cancer Institute had projected breast cancer (BC) as one of the topmost prevalent malignancies around the globe. In many cases, BC becomes resistant to chemotherapy, radiation and hormonal therapies. Traditional BC therapies are associated with adverse side effects, drug resistance and recurrence. Extensive research work has shown that these dietary phytochemicals (DPs) may exert therapeutic effects by regulating the miRNA expression. A large number of DPs have been researched as miRNA regulatory agents against BC and some other DPs have not yet been tested against BC. We have discussed the effects of curcumin, diallyl disulphide, 3,3′ diindolylmethane, ellagic acid, genistein, indole-3-carbinol, quercetin, resveratrol, and sulforaphane on regulation of expression of BC miRNAs in a wide range of in vitro and in vivo models. We have also shown some of the possible DPs (Oleanolic acid, capsaicin, benzyl isothiocyanate, epigallocatechin gallate, phenethyl isothiocyanate and ursolic acid) that have shown miRNA regulatory activities and have not yet been tested against BC miRNAs. Finally, current limitations, challenges, future perspectives of DPs and BC research are also critically discussed.

Cancer is a frightful disease and represents one of the biggest health-care issues for the human race and demands a proactive strategy for cure. Plants are reservoirs for novel chemical entities and provide a promising line for research on cancer. Hitherto, being effective, chemotherapy is accompanied by certain unbearable side effects. Nevertheless, plants and plant derived products is a revolutionizing field as these are Simple, safer, eco-friendly, low-cost, fast, and less toxic as compared with conventional treatment methods. Phytochemicals are selective in their functions and acts specifically on tumor cells without affecting normal cells. Carcinogenesis is complex phenomena that involves many signaling cascades. Phytochemicals are considered suitable candidates for anticancer drug development due to their pleiotropic actions on target events with multiple manners. The research is in progress for developing potential candidates (those can block or slow down the growth of cancer cells without any side effects) from these phytochemicals. Many phytochemicals and their derived analogs have been identified as potential candidates for anticancer therapy. Effort has been made through this comprehensive review to highlight the recent developments and milestones achieved in cancer therapies using phytomolecules with their mechanism of action on nuclear and cellular factors. Furthermore, drugs for cancer treatment and their limitations have also been discussed.

Objective To study the seroprevalence of hepatitis B virus (HBV) and hepatitis delta virus (HDV) infections in patients visiting outpatient department of a major tertiary care hospital in Khyber Pakhtunkhwa region of Pakistan. Methods Blood samples were collected from non-hospitalized patients. Serological analysis was done by ELISA and viral DNA was amplified by PCR. The amplified DNA was analyzed by agarose gel electrophoresis. Results Altogether, 946 blood samples were screened, overall percentage of HBsAg-positive patients remained 22.41% (prevalence: 224.10/1 000; CI: 0.197 5 ± 0.250 7) with the highest incidence rates among relatively younger age groups (20–29 years). The prevalence of HBV–HDV co-infection was found to be 46.75/1 000; CI: 0.031 8 ± 0.061 7. In HBsAg-positive patients, anti-HBc-total was detected in 86.79% while 25.00% were positive for anti-HBc-immunoglobulin M. Similarly, among these patients, HBV DNA was detected in 64.13% and 10.85% were co-infected with HDV. Different symptoms were associated with the prevailing infection, including malaise (62%), anorexia (66%) and fatigue (73%). The most commonly associated symptom was abdominal discomfort. Among these patients, certain risk factors, including surgery, visit to dentist and intravenus infusions were frequently associated with the infection (χ

Objective: To scrutinize patterns of multi-drug-resistant uropathogenic Escherichia coli (UPEC) strains and particularly of fluoroquinolone-resistance this is an alternative choice for the treatment of urinary tract infections. Methods: Bacterial samples (n = 250) were collected from out-patients from August 2012 to August 2014 Islamabad. Antibiotic susceptibility profiling and determination of minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations were performed according to the guidelines of Clinical and Laboratory Standards Institute (CLSI, 2012). Genes, qnrA, qnrB and qnrS were identified by DNA amplification and sequencing. Results: The highest percentage of UPEC isolates were resistant to co-trimoxazole (82%) followed by cephalothin (80%), 2nd Gen, 3rd Gen and 4th Gen cephalosporins, respectively. Resistance against gentamicin, amikacin remained 29% and 4%. For other drugs including nitrofurantoin, tetracycline, carbapenem and beta-lactam inhibitors remained below 10%. Altogether, 59% of the isolates were resistant to at least three antibiotics including one fluoroquinolone. Overall, MICs for ciprofloxacin remained (MIC ≥ 256 μg/mL) and for levofloxacin (MIC ≥ 16 μg/mL and 32 μg/mL). No significant differences were observed regarding MIC values of extended spectrum β-lactamase (ESBL) and non-ESBL producers. For qnrS and qnrB positive isolates MICs remained above 32 μg/mL. Prevalence of UPEC was significantly higher among females and 40% of the isolates were ESBL producers. Conclusions: Higher percentages of ESBL producing UPEC were associated with urinary tract infections. Moreover, the majority of these isolates were multi-drug resistant and fluoroquinolone-resistant.