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Ras-associated binding (Rab) GTPases control diverse stages of endo and exocytic pathways. Functional impairments of Rabs and its associated proteins have been implicated in many hereditary and neurological diseases. Although Rabs are not classically considered as oncoproteins, many Rabs have been involved in tumor progression/proliferation and its aggressiveness. Rabs contribute to tumor cell migration, invasion of cancer cell to extracellular matrix (ECM) and modification of tumor microenvironment through modulation in integrin trafficking, exosomal and protease secretions. In the present review, current knowledge about the pathogenesis and tumor progression of some Rabs (Rab27, 25 & 21) has been discussed.

Tyrosinase is a key enzyme in melanogenesis and its high activity leads to increasedpigmentations causing skin disorder like freckles, melanosoma and black spot. Therefore to search for new tyrosinase inhibitors is desirable. In present study, methanolic (MeOH) extracts from leaves, fruit peel and pulp of Citrus bergamia (CB) and, leaves and fruitof Ficus carica (FC) were prepared which were further process for fractional ethyl alcohol (EA), n-hexane (n-Hx) and chloroform (CHCl3)extractions (total 20 extracts) aiming to test their anti-tyrosinase potential, in-vitro. Our results confirmed that all MeOH FC and CB extracts showed significant anti-oxidant activity with IC50 range of 461.9 ± 16.1µg/ml to 2324.4 ± 116.1 µg/ml. Moreover, CB and FC all 20 extracts have significant anti-tyrosinase activity with IC50 range of 13.9 ± 0.5 µg/ml to 320.5 ± 3.3 µg/ml. Interestingly, CB MeOH-EA peel and leaf extracts showed tyrosinase inhibition (IC50) 13.9 ± 0.5 µg/ml and 17.2 ± 0.8 µg/ml, respectively) is better than all other tested extracts and positive control kojic acid (IC50=18.75±5.29µg/ml). Thus, CB MeOH-EA peel extract with lowest IC50 value among all the tested extracts and kojic acid is proposed as potent candidate to control tyrosinase rooted hyperpigmentation.

Living in an era of industrialization, there is an utmost need to replace chemical catalysts with biocatalysts owing their cost effectiveness, milder reaction conditions, eco-friendly nature and specificity. α-amylase is one of the top commercial enzymes of industrial importance. It hydrolyzes internal α (1, 4) glycosidic linkages in polysaccharides and yields oligosaccharides of varying length. The aim of present study was to clone and express α-amylase from a novel specie Enterobacter xiangfangensis. Amplified product was cloned by A and T overhangs and transformed into cloning host; E. coli DH5α cells. Gene encoding α-amylase (1488bp) was sequenced to confirm the adequate amplification, digested with BamH1 and Xho1, cloned into expression vector; pET28b (+) and transformed into expression host; E. coli strain BL21 CodonPlus (DE3) cells. The expression of α-amylase was induced by IPTG and optimized with varying IPTG concentrations and its induction intervals. The maximum expression was observed after 8 hours of 1mM IPTG induction. The results showed that α-amylase from novel specie, Enterobacter xiangfangensis has a potential to expresses itself in heterologous expression system so this recombinant α-amylase is ray of hope for enormous downstream applications.

Due to social and geographical mobility and globalization, many minority languages in the world are pushed to the periphery. Reasons for such a trend differ among languages. In the case of the Punjabi language, despite being spoken by a major portion of the population, the speakers are gradually disowning it. Considering this gradual shift, the present study explores the predicament of the Punjabi language. The study uses phenomenological design and collects data from Punjabi ethnic students in four different universities in Islamabad. The study uses semi-structured interviews, TV shows, and natural conversations. Findings reveal that the Punjabi speakers themselves disown their language as well as Punjabi identity due to social, economic, religious, and political reasons. Especially women avoid the language more, they do not speak Punjabi with their children, and they reject their Punjabi identity.

In the present study, a series of azo derivatives (TR-1 to TR-9) have been synthesised via the diazo-coupling approach between substituted aromatic amines with phenol or naphthol derivatives. The compounds were evaluated for their therapeutic applications against alpha-glucosidase (anti-diabetic) and pathogenic bacterial strains E. coli (gram-negative), S. aureus (gram-positive), S. aureus (gram-positive) drug-resistant strain, P. aeruginosa (gram-negative), P. aeruginosa (gram-negative) drug-resistant strain and P. vulgaris (gram-negative). The IC50 (µg/mL) of TR-1 was found to be most effective (15.70 ± 1.3 µg/mL) compared to the reference drug acarbose (21.59 ± 1.5 µg/mL), hence, it was further selected for the kinetic studies in order to illustrate the mechanism of inhibition. The enzyme inhibitory kinetics and mode of binding for the most active inhibitor (TR-1) was performed which showed that the compound is a non-competitive inhibitor and effectively inhibits the target enzyme by binding to its binuclear active site reversibly.

Tyrosinase is a key enzyme of melanogenesis which determines the mammalian skin, hair and eye colour. Hyper-pigmentation leads to various skin disorders like melasma, sunspots, age spots and freckles. Moreover, abnormal skin pigmentation is a serious aesthetic concern which leads to psychosocial problems. Thus to achieve melanin inhibition, inhibition of tyrosinase might be an effective approach. To this end we prepared methanolic (MeOH) extracts from leaves and roots of Allium sativum (AS) and Mentha piperita (MP), which were further processed for 1:1 fractional distillation to prepare methanolic n-hexane (MeOH_n-Hx), methanolic ethyl acetate (MeOH_EA) and methanolic chloroform (MeOH_CHCl3) extracts, aiming to evaluate tyrosinase and anti-oxidant activities in-vitro. Our results confirmed that all MeOH-crude AS and MP extracts showed significant anti-oxidant activity with IC50 values ranging from 0.05 ± 0.2 mg/ml to 4.3 ± 2.3mg/ml. Moreover, AS and MP all 16 extracts have significant anti-tyrosinase activity with IC50 range from 0.014 ± 0mg/ml to 1.205 ± 0.07mg/ml. Interestingly, AS leaf MetOH_EA, AS leaf MetOH_CHCl3, AS root MetOH_EA and MP leaf MetOH_CHCl3 showed significant anti-tyrosinase activity even higher than positive control kojic acid. AS leaf MetOH_CHCl3 extract being the most potent among all tested extracts is proposed as potential candidate to treat tyrosinase rooted hyper-pigmentation in future.

Recently, screening of efficient urease inhibitors by employing organic small molecules metalloderivatives interests the scientific community due to their efficacy for treatment of urease triggered health complications. This study comprises the synthesis, urease inhibition activity, optical analysis and molecular modeling of hydrazinecarbothioamide and hydrazinecarboxamide metalloderivatives. Characterization of synthesized materials was done by UV-visible, fluorescence, NMR and FTIR spectroscopic analysis. Metalloderivatization of ligands induce increment in urease inhibition potential and effect was prominent for copper complexes with 10-fold enhancement, cobalt complex with 3.5 fold's enhancement and palladium with 2-fold increment in the inhibition efficacy toward urease when it was compared with reference urease inhibitor. Zinc and iron complexes cause declined urease inhibition activity of the bare ligand. The overall activity of hydrazinecarbothioamide slightly exceeds than that of hydrazinecarboxamide, possibly due to larger complexation ability of sulfur-based ligand in comparison to oxygenated derivatives i.e., hydrazinecarboxamide. The enzyme inhibition kinetics for the most active complexes represent the mixed type urease inhibition for 3a and competitive urease inhibition for 5a, as determined by Lineweaver-Burk plots. The docked scoring values for both the ligands were calculated to be 61.34, 64.72, 56.68, 62.94, 64.98 and 58.98. Three active hydrogen bonds were observed in docking complex upon computational analysis of most potent metallodrug 3a inside active region of targeted protein.

The review summarizes the recent (2016-2019) practical applications of novel extraction methods for Citrus metabolite extraction, such as microwave-assisted (MAE), ultrasound-assisted (UAE), super-critical carbon dioxide (SC-CO2) and enzyme-assisted extraction (EAE) with the aim to compare efficiencies based on the criteria of enhanced (%) yield, cost-effectiveness, reproducibility, eco-friendliness, time/energy consumed and industrial scale application. It was found that supercritical carbon dioxide extraction (SC-CO2) is the most successful and scaled-up technique when compared to MAE, UAE, Soxhlet and EAE, following the trend: SC-CO2 > EAE > UAE > MAE. However, other novel approaches, including pulse-electric field (PEF), sub-critical water extraction (SWE), solarenergy assisted extraction (SE) and molecularly imprinted polymers (MIPs), that have not been well explored for Citrus bioactives extraction, have the potential to be coupled with conventional as well as contemporary methods leading to an innovative hypothetical scaled-up design.

Synthetic heterocyclic compounds have incredible potential against different diseases; pyridines, phenolic compounds and the derivatives of azo moiety have shown excellent antimicrobial, antiviral, antidiabetic, anti-melanogenic, anti-ulcer, anticancer, anti-mycobacterial, anti-inflammatory, DNA binding and chemosensing activities. In the present review, the above-mentioned activities of the nitrogen-containing heterocyclic compounds (pyridines), hydroxyl (phenols) and azo derivatives are discussed with reference to the minimum inhibitory concentration and structure–activity relationship, which clearly indicate that the presence of nitrogen in the phenyl ring; in addition, the hydroxyl substituent and the incorporation of a diazo group is crucial for the improved efficacies of the compounds in probing different diseases. The comparison was made with the reported drugs and new synthetic derivatives that showed recent therapeutic perspectives made in the last five years.

Recurrent Laryngeal papillomatosis (RLP) is a disease of the aero-digestive junction superimposed at the upper respiratory tract. Low risk human papillomavirus type 6 and 11 are infectious agents in RLP. Mainstay of treatment for RLP is CO2 laser vaporization for debulking of papilloma. Understanding of the gene changes at expression level might prove helpful for RLP management. The study was designed to evaluate the changes in tumorigenesis genes in RLP cases to mark the severity and aggression at gene expression level for disease management. Tissue samples and peripheral blood samples were acquired from clinically diagnosed RLP patients of age

Two new sphingolipids, stewartins A: [(2S,3S,4R)-2-{[(2R,11E)-2-hydroxyoctadec-11-enoyl]amino}tetraeicosane-1,3,4-triol-1-O-β-D-glucopyranoside, 1] and B: [(2S,3S,4R)-2-{[(2R,11E)-2-hydroxyeicos-11-enoyl]amino}tetraeicosane-1,3,4-triol-1-O-β-glucopyranoside, 2], along with nine known compounds (3–11) were isolated from the n-hexane soluble fraction of the methanolic extract of the whole plant of Phlomis stewartii. Compounds 1, 2, 4, and 6 showed inhibitory potential against the enzyme lipoxygenase (LOX) in a concentration-dependent manner with IC50 values ranging between 42.2 ± 0.2 to 55.7 ± 0.8 μM, whereas compounds 3, 5, and 7–11 showed inhibition against enzyme the α-glucosidase with IC50 values between 201.4 ± 0.6 to 277.7 ± 0.3 μM, respectively.

Colorectal cancer is a life-threatening and therapeutically challenging disease. Increasingly it is being deciphered that genetic and epigenetic mutations play a central role in cancer onset and progression. Excitingly, discovery of non-coding RNAs is considered to be a milestone in molecular oncology and emerging evidence is deepening our understanding about pivotal role of miRNAs in carcinogenesis. miR-143 has been experimentally verified to play an instrumental role as tumor suppressor. Recent studies suggest that single nucleotide polymorphisms rs41291957 and rs353292 in miR-143 may associate with the progression and or development of colorectal cancer. In present study 400 Pakistani subjects participated including 200 colorectal cancer patients and 200 age and gender matched healthy individuals. Blood samples and clinical information of the confirmed patients was collected from cancer diagnosis and treatment hospitals in Pakistan. The polymorphisms rs41291957 and rs353292 were genotyped in patients and controls by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and results were validated by Sanger sequencing. The association of the SNPs within the study group was analyzed by χ² test with p value < 0.05 as significant. Odds ratio was calculated with 95% confidence interval.Genetic predisposition to cancer was observed in presence of characteristic rs45291957 polymorphism. χ² test results show strongly significant association mi-RNA rs45291957 SNP with colorectal cancer p value 0.0111 (

Objective To determine the relationship between physical activity and depression between the two genders amongst the young adults of Islamabad. Methods We conducted a cross-sectional study of students who were studying in various colleges and universities of Islamabad. Students who were willing to participate in the study and who were studying in the institute for more than six months were included in the study. The data was collected through a self-reporting questionnaire and a self-constructed questionnaire. Cronbach's alpha was used to assess the internal consistency of the self-constructed questionnaire, and it was found to be 0.69. The data obtained were analyzed on IBM's Statistical Package for the Social Sciences (SPSS) version 21 (IBM, Armonk, NY, US). Results Out of 298 participants, 113 (38%) were males and 185 (62%) were females. The mean age of the participants was 21.60±1.39 years. One-hundred twenty-six participants were found most likely to suffer from depression. Out of these 126 participants, 42 (33%) were females and 84 (67%) were males. Thirty-nine percent of the participants reported fatigue and inability to attend to their normal routine. Pearson correlation was calculated for the association of depression and age, and it was found to be significant (p-value less than 0.05). The correlation for depression with respect to physical activity was also found to be significant (p-value less than 0.05). Conclusions Low levels of physical activity can be a major risk factor for the development of depression and the possible exacerbation of any pre-existing mental disorder. There is a need to combat this problem to decrease the use of pharmaceutical means for curing depression.

Plants are a rich source of bio-functional phytochemicals. The present study was designed to investigate the methanol extracts of selected plants for their phytochemicals, antioxidant activity, urease and acetylcholine esterase (AChE) inhibitory potential.

Based on the previous reports on α-glucosidase inhibitory activity of benzimidazole class, we intend to evaluate further this class as potential inhibitors of α-glucosidase enzyme. Thus, in the current study synthesis of 5-bromo-2-aryl benzimidazole derivatives 1–25 was carried out. All the synthetic compounds were characterized by different spectroscopic techniques EIMS, HRMS, 1H-NMR, and 13C-NMR. Molecular docking was also performed on the selected compounds 1, 4, 7, and 17 having varying substitution pattern in order to understand the molecular interaction of molecules with the active site of the enzyme. All compounds were evaluated for their in vitro α-glucosidase inhibitory activities. Twenty-three compounds out of twenty-five showed excellent to moderate activity in the range of IC50 = 12.4–103.2 μM. Inhibitory results were compared with the standard drug acarbose (IC50 = 38.25 ± 0.12 μM). Compounds 1 (IC50 = 37.82 ± 0.08 μM), 9 (IC50 = 37.76 ± 0.05 μM), 12 (IC50 = 24.96 ± 0.09 μM), 16 (IC50 = 21.15 ± 0.08 μM) and 17 (IC50 = 8.34 ± 0.02 μM) showed excellent inhibition as compared to standard drug acarbose (IC50 = 38.25 ± 0.12 μM). Especially, 17 (IC50 = 8.34 ± 0.02 μM) was found to be five-fold more active than the standard.

In this review, specific therapeutic and medicinal advantages including antiviral, antibacterial, antifungal and antitumor, strategies for drug designing, structure-activity relationship, advances in the syntheses of azo and hippuric acid derivatives of more than 50 compounds have been discussed since 2009-2018. It is found that phenyl-diazenyl azo derivatives and pyridinyl substituted hippuric acid derivatives showed promising antiretroviral potential. The incorporation of azo functionality to the respective quinolones and coumarin moieties and the insertion of thiocarbazone to hippuric acid displayed immense antibacterial activities. While, azo and hippuric acid derivatives of triazole and phenyl species gave maximum fungicidal as well as cytotoxic activities.