Artemisia amygdalina Upregulates Nrf2 and Protects Neurons Against Oxidative Stress in Alzheimer Disease.

Alzheimer disease is a complex neurodegenerative disorder. It is the common form of dementia in elderly people. The etiology of this disease is multifactorial, pathologically it is accompanied with accumulation of amyloid beta and neurofibrillary tangles. Accumulation of amyloid beta and mitochondrial dysfunction leads to oxidative stress. In this study, neuroprotective effect of Artemisiaamygdalina against H2O2-induced death was studied in differentiated N2a and SH-SY5Ycells. Cells were treated with H2O2 to induce toxicity which was attenuated by Artemisia amygdalina. The nuclear factor erythroid 2-related factor 2 (Nrf2) is an emerging regulator of cellular resistance to oxidants. It controls the basal and induced expression of antioxidant response element-dependent genes. Further, we demonstrated that Artemisia amygdalina protects neurons through upregulation of Nrf2 pathway. Moreover, reactive oxygen species and mitochondrial membrane potential loss formed by H2O2 was attenuated by Artemisia amygdalina. Thus, Artemisia amygdalina may have the possibility to be a therapeutic agent for Alzheimer disease.

Psychosocial correlates of prolonged postpartum depression in mothers of children with movement disorders: cross-sectional study from a paediatric developmental rehabilitation centre in Peshawar.

OBJECTIVE: To identify potential predictors of prolonged postpartum depression in mothers of children with physical disabilities. METHODS: The cross-sectional, correlational study was conducted at a paediatric neurodevelopmental rehabilitation centre in Peshawar, Pakistan, from December 9, 2016, to January 23, 2017, and comprised mothers of children with movement disorders born between January, 2014, and June, 2016. Prolonged postpartum depression was defined as onset of maternal depression between 6 and 36 months after birth. Edinburgh Postnatal Depression Scale was used with a cut-off score of 13/30, while a pretested questionnaire examined risk and protective factors predicting prolonged postpartum depression using binary logistic regression. SPSS 20 was used for data analysis. RESULTS: There were 171 subjects with a mean age of 27±6.4 years. Among them, prolonged postpartum depression was found in 95(55.6%). Six significant predictors of the condition were identified: supportive husband, child's disability having negative effect on social ties, daily physical help in childcare by at least one family member, pregnancy-induced hypertension, mother being blamed for child's disability, and financial problems (p<0.05 each). CONCLUSIONS: The identified predictors specific to local settings played a distinctive role in prolonged post-partum depression occurrence, particularly in the context of disability.

Alpha-1-antitrypsin deficiency: Genetic variations, clinical manifestations and therapeutic interventions.

Alpha-1-antitrypsin (AAT) is an acute phase secretory glycoprotein that inhibits neutrophil proteases like elastase and is considered as the archetype of a family of structurally related serine-protease inhibitors termed serpins. Serum AAT predominantly originates from liver and increases three to five fold during host response to tissue injury and inflammation. The AAT deficiency is unique among the protein-misfolding diseases in that it causes target organ injury by both loss-of-function and gain-of-toxic function mechanisms. Lack of its antiprotease activity is associated with premature development of pulmonary emphysema and loss-of-function due to accumulation of resultant aggregates in chronic obstructive pulmonary disease (COPD). This' in turn' markedly reduces the amount of AAT that is available to protect lungs against proteolytic attack by the enzyme neutrophil elastase. The coalescence of AAT deficiency, its reduced efficacy, and cigarette smoking or poor ventilation conditions have devastating effect on lung function. On the other hand, the accumulation of retained mutant proteins in the endoplasmic reticulum of hepatocytes in a polymerized form rather than secreted into the blood in its monomeric form is associated with chronic liver disease and predisposition to hepatocellular carcinoma (HCC) by gain- of- toxic function. Liver injury resulting from this gain-of-toxic function mechanism in which mutant AAT retained in the ER initiates a series of pathologic events, eventually culminating at liver cirrhosis and HCC. Here in this review, we underline the structural, genetic, polymorphic, biochemical and pathological advances made in the field of AAT deficiency and further comprehensively emphasize on the therapeutic interventions available for the patient.

Development of Cefotaxime Impregnated Chitosan as Nano-antibiotics: De Novo Strategy to Combat Biofilm Forming Multi-drug Resistant Pathogens.

Frequent incidents of antibiotic-resistant biofilm forming pathogens in community-associated and hospital-acquired infections have become a global concern owing to failure of conventional therapies. Nano-antibiotics (NABs) are de novo tools to overcome the multi-drug resistant mechanisms employed by the superbugs. Inhibition of biofilm formation is one of those strategies to curb multi drug resistance phenomenon. In the current study, the anti-biofilm and antibacterial potential of newly synthesized cefotaxime loaded chitosan based NABs have been investigated. Both bare and cefotaxime loaded NABs were prepared by ionotropic gelation method. They were found carrying positive zeta potential of more than +50 mV, indicating highly stable nano-dispersion. Moreover, microscopic studies revealed their size as less than 100 nm. NABs were tested against clinical isolates of multi drug resistant Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and methicillin resistant Staphylococcus aureus and wherein they demonstrated broad-spectrum anti-biofilm and anti-pathogenic activity. Thus, in vitro synergistic action of cephalosporin drugs and chitosan polymer at nano-scale in contrast to free antibiotics can be an improved broad-spectrum strategy to thwart resistance mechanisms in both Gram-positive and Gram-negative resistant pathogens.

Cefazolin loaded chitosan nanoparticles to cure multi drug resistant Gram-negative pathogens.

Antibiotic resistance against Gram-negative microbes is considered as an alarming phenomenon that needs to be addressed urgently to develop better therapeutic solutions. The aim of the present research work was to investigate and develop cefazolin loaded chitosan nanoparticles (CSNPs) as a potential tool against multidrug resistant pathogens. Empty and drug loaded CSNPs were prepared by ionic gelation method. It was observed by Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) based studies that CSNPs were less than 100 nm in size and displayed homogeneity both in shape and size. Encapsulation of cefazolin has not increased the size of nano systems. Zeta sizer results revealed that both systems have positive zeta potential of more or less +50 mV, thus contributing towards a stable formulation. Encapsulation efficiency was directly proportional to the increase in the concentration of antibiotic (28-62%). Furthermore, growth kinetics study had demonstrated excellent antimicrobial potential of cefazolin loaded CSNPs against multi drug resistant Klebsiella pneumoniae, Pseudomonas aeroginosa and Extended Spectrum Beta Lactamase (ESBL) positive Escherichia coli.