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Liver plays vital role in detoxification of exogenous and endogenous chemicals. These chemicals as well as oxidative stress may cause liver disorders. This study was aimed to evaluate the hepatoprotective effects of various fractions of Aconogonon alpinum methanolic extract against carbon tetrachloride (CCl4)-induced liver toxicity in mice. First, hepatoprotective potential of various fractions of A. alpinum was assessed and then antioxidant activity and profiling of polyphenolic compounds were assessed. A total of 78 male albino mice (BALB/c) were randomly divided into 13 groups (n = 6); Group I (normal control), Group II (CCl4 only), Group III (CCl4 + silymarin 100 mg/kg) and Groups IV–XIII (CCl4 + various fractions [200 and 400 mg/kg]). Hepatic biochemistry and liver injury were assessed by analysis of serum levels of hepatic enzymes and histopathological analysis, respectively. Results showed that polar fractions (ethyl acetate, n-butanol and aqueous fractions) exhibited highly significant (P < 0.01) reduction in increased level of liver biochemical parameters in a dose-dependent manner with consistent histopathological findings. Likewise, these fractions revealed strong antioxidant potential and polyphenolic compound contents. In conclusion, the present work has revealed promising antioxidant activity, polyphenolic profiling and potential hepatoprotective efficacy. Thus, the significant results unveil the study as a step forward towards evidence-based phytomedicine.

ESBL producingEnterobacteriacae harbouring multidrug-resistant plasmids is an emerging worldwide threat. One of the major concerns is the prevalence of plasmid-mediated quinolone resistance (PMQR) to Quinolones which has hindered the viability of these antibiotics. To date, very little data is available regarding the co-existence of ESBL and PMQR in Pakistan. This study aimed to detect PMQR genes in clinical isolates of ESBL producing Enterobacteriaceae in the city of Rawalpindi. A total of 60 clinical ESBL positive Enterobacteriaceae isolates were obtained from hospitalized patients at Holy family Hospital, Rawalpindi. It included strains of E. coli (n=24), K. pneumoniae (n=25), and Enterobacter spp (n=11). Antimicrobialsusceptibility was determined by the standard disk diffusion method. Genes encoding quinolone resistance (qnrA, qnrB and qnrS) were detected using PCR. Out of 60 tested strains, 38 (63%) yielded PMQR determinants. QnrB was the most prevalent occurring alone and in combination with other qnr genes in about 89% (34/38) of the ESBL producing isolates. It was followed by qnrS (22/38 i.e 58%) and qnrA (12/38 i.e 32%). E.coli was the predominant qnrA (43%) and qnrS (69%) harbouring species.

To identify the underlying genetic anomalies in two consanguineous Pakistani families with autosomal recessive achromatopsia.The exploratory study was conducted under the patronage of International Islamic University, Islamabad, Pakistan, and Sungshin Women University, Seoul, South Korea, after two families coded PKCN-02 and PKCN-07 belonging to different ethnic groups were recruited from different areas of Khyber Pakhtunkhawa province of Pakistan in July 2016. The families were originally diagnosed with nystagmus upon medical examination. Exome sequencing was performed to identify the possible causative gene which was found to be cyclic nucleotide-gated channel alpha-3. Sanger sequencing was performed to confirm the mutations. After genetic analysis, clinical analysis was re-evaluated for colour vision using Ishihara 26 plates. Pathogenic potential of these mutations was evaluated using algorithmic mutation prediction tools. In-silico analysis was performed to predict effect of these mutations on protein structure of the gene in question.Exome sequencing revealed a reported missense mutation c .1306CT (p.R436W) in family PKCN-02 and a novel missense mutation c.1540GA (p.D514N) in family PKCN-07. After mutational analysis, clinical re-evaluation revealed that both families were segregating autosomal recessive achromatopsia. Further, the topological model of the cyclic nucleotide-gated channel alpha-3 polypeptide describes these missense mutations primarily affecting the C-linker and cyclic guanosine monophosphate-binding sites, respectively. Protein structure modelling of cyclic nucleotide-gated channel alpha-3 protein revealed abnormal structure produced by p.R436W and p.D514N..Exome sequencing approach was used to first identify the genetic alteration in families with nystagmus. Two mutations in cyclic nucleotide-gated channel alpha-3gene were uncovered, including one novel mutation. Clinical re-evaluation uncovered that both families had achromatopsia.

Metabolism refers to a chain of chemical reactions converting food/fuel into energy to conduct cellular processes, including the synthesis of the building blocks of the body, such as proteins, lipids, nucleic acids, and carbohydrates, and the elimination of nitrogenous wastes. Metabolic chain reactions are catalyzed by various enzymes that are orchestrated in specific pathways. Metabolic pathways are important for organisms to grow and reproduce, maintain their structures, and respond to their environments. The coordinated regulation of metabolic pathways is important for maintaining metabolic homeostasis. The key steps and crucial enzymes in these pathways have been well investigated. However, the crucial regulatory factors and feedback (or feedforward) mechanisms of nutrients and intermediate metabolites of these biochemical processes remain to be fully elucidated. In addition, the roles of these enzymes and regulatory factors in controlling metabolism under physiological and pathological conditions are largely unknown. In particular, metabolic dysregulation is closely linked to the development of many diseases, including obesity, fatty liver, diabetes, cancer, cardiovascular, cerebrovascular, and neurodegenerative diseases. Therefore, metabolism, an old area of biochemistry, has attracted much attention in the last decade. With substantially increased government funding, the involvement of talented researchers, an improved infrastructure and scientific environment over the last ten years, the basic research in the field of metabolism in China has dramatically advanced. Here, we have summarized the major discoveries of scientists in China in the last decade in the area of metabolism. Due to the vast amount of information, we focused this review on specific aspects of metabolism, particularly metabolic regulation and lipid metabolism in vertebrates. © 2016 IUBMB Life, 68(11):847-853, 2016.

Chronic Hepatitis C Virus (HCV) infection is still a major health issue especially in endemic areas where fewer direct-acting virals (DAAs) are treatment options. Some HCV variants are associated with resistance and it reduces DAAs success where pre-existing variants prevail. In this study, we investigated resistance-associated polymorphisms (RAPs) in the HCV NS3 region from DAAs naïve Pakistani patients. 277 chronic HCV treatment naïve patients infected with genotype 1a, 3a and 3b were selected from various clinical centers in the capital city of Khyber Pakhtunkhwa province Pakistan. All the patients were included in this study after taking informed consent. HCV NS3 region was amplified and Sanger sequencing was performed to analyze RAPs to NS3 protease inhibitors. Of the total 29.24% (81/277) patients had detected with known RAPs viz V36A/G/L, T54S, V55A/D/I, Q80K/R, S122G/T/R, R155K/T/I, V158I, D168T/Q, and I170V. Among HCV-1a subjects overall RAPs found were 26.09% (12/46) and most prevalent substitutions were V36A/G (10.87%, 5/46) and R155K/T/I (8.70%, 4/46). Of the total HCV-3a infected patients, 30.95% were observed with RAPS. Ammon these, the most frequent substitutions were Q80R (13.69%, 23/168) followed by V36L (18.33%, 14/168) and V55I (5.95%, 10/168). Among HCV-3b patients, 26.98% were found with RAPs and S122R and Q80R were the dominant variants detected in 17.46 (11/63) and 12.70% (8/63) patients respectively. All these substitutions were associated with Boceprevir, Simeprevir, Telaprevir, and Paritaprevir. Single substitution in one sequence was found in 18.77% (52/277) and multiple in 10.46% (29/277). More than one RAP was frequent in HCV-3a sequences. Natural RAPs are common in chronic HCV patients infected with genotype 1a, 3a and 3b, the most prevalent subtypes in Pakistan. High prevalence of HCV NS3 RAPs suggested a large scale study of the NS3 gene before the introduction of NS3 protease inhibitors in Pakistan.

Periodic monitoring of physiological data of inward patients' is a way to keep their health conditions under control. For this purpose, the medical staff record patients' vital signs periodically. Such an approach is exhaustive and may not be safe for patients because in some cases, a slight negligence from health care staff may lead to serious consequences for the patients. This paper suggests a MPI cluster based distributed computing framework in which newly surfaced low cost single board computers called Raspberry Pi is used for continuous monitoring of in-ward patients' vital sign data and sending them to the hospital server for doctors' observation and data logging. Alert signals may be triggered in case of any vital sign data exceeding some predefined dangerous limits. Furthermore, the hospital server can be accessed through Internet for remote monitoring of real time physiological data.

In emergencies or life-threatening situations, patients are generally shifted to hospitals in ambulances. The health conditions of on-board patients can become critical if they are not evaluated and treated in time. Chances of saving lives can increase significantly if patients’ vital signs inside an ambulance or on-site triage area are transferred to a hospital in real time. If the ambulances are linked to target hospitals, then the physicians in emergency rooms can monitor on-board patients’ vital signs and issue instructions to paramedics to stabilize patients’ medical conditions before they reach the assigned hospitals. Transferred vital signs data may also be archived for medical records. The Internet of things (IoT) is a paradigm which envisions Internet connectivity of virtually everything on the earth. In this paper, an IoT-based low-cost solution is proposed to monitor, archive, analyze, and tag the vital signs data of multiple patients and transfer them to the remote hospital in real time. This opens up a lot of possibilities in telemedicine and disaster management. As a proof of concept, the functionality of the proposed system was validated by developing a prototype model utilizing an IoT-enabled medical sensor board and a Linux server mimicking the remote hospital server. Results of actual data transmission obtained during experimentation are also provided. It is hoped that the proposed system can play a role in saving human lives in disaster situations.

Metabolism refers to a chain of chemical reactions converting food/fuel into energy to conduct cellular processes, including the synthesis of the building blocks of the body, such as proteins, lipids, nucleic acids, and carbohydrates, and the elimination of nitrogenous wastes. Metabolic chain reactions are catalyzed by various enzymes that are orchestrated in specific pathways. Metabolic pathways are important for organisms to grow and reproduce, maintain their structures, and respond to their environments. The coordinated regulation of metabolic pathways is important for maintaining metabolic homeostasis. The key steps and crucial enzymes in these pathways have been well investigated. However, the crucial regulatory factors and feedback (or feedforward) mechanisms of nutrients and intermediate metabolites of these biochemical processes remain to be fully elucidated. In addition, the roles of these enzymes and regulatory factors in controlling metabolism under physiological and pathological conditions are largely unknown. In particular, metabolic dysregulation is closely linked to the development of many diseases, including obesity, fatty liver, diabetes, cancer, cardiovascular, cerebrovascular, and neurodegenerative diseases. Therefore, metabolism, an old area of biochemistry, has attracted much attention in the last decade. With substantially increased government funding, the involvement of talented researchers, an improved infrastructure and scientific environment over the last ten years, the basic research in the field of metabolism in China has dramatically advanced. Here, we have summarized the major discoveries of scientists in China in the last decade in the area of metabolism. Due to the vast amount of information, we focused this review on specific aspects of metabolism, particularly metabolic regulation and lipid metabolism in vertebrates. © 2016 IUBMB Life, 68(11):847-853, 2016.