Co-expression of HIF-1α, MDR1 and LAPTM4B in peripheral blood of solid tumors

The hypoxic tumor microenvironment is the major contributor of chemotherapy resistance in solid tumors. One of the key regulators of hypoxic responses within the cell is the hypoxia inducible factor-1α (HIF-1α) that is involved in transcription of genes promoting cell survival and chemotherapy resistance. Multidrug resistance gene-1 (MDR1) and Lysosome-associated protein transmembrane 4B-35 (LAPTM4B-35) are among those notable players which augment their responses to cellular hypoxia. MDR1 is the hypoxia responsive gene involved in multidrug resistance phenotype while LAPTM4B-35 is involved in chemotherapy resistance by stabilizing HIF-1α and overexpressing MDR1. Overexpression of HIF-1α, MDR1 and LAPTM4B has been associated with poor disease outcome in many cancers when studied individually at tissue level. However, accessibility of the tissues following the course of chemotherapy for ascertaining chemotherapy resistance is difficult and sometimes not clinically feasible. Therefore, indication of hypoxic biomarkers in patient’s blood can significantly alter the clinical outcome. Hence there is a need to identify a blood based marker to understand the disease progression. In the current study the expression of hypoxia associated chemotherapy resistance genes were studied in the peripheral blood lymphocytes of solid tumor patients and any potential correlation with disease progression were explored. The expression of HIF-1α, MDR1 and LAPTM4B was studied in blood of 72 breast, 42 ovarian, 32 colon and 21 prostate cancer patients through real time PCR analysis using delta cycle threshold method. The statistical scrutiny was executed through Fisher’s Exact test and the Spearman correlation method. There was 12–13 fold increased in expression of HIF-1α, two fold increased in MDR1 and 13–14 fold increased in LAPTM4B mRNA level in peripheral blood of breast, ovarian, prostate and colon cancer patients. In the current study there was an association of HIF-1α, MDR1 and LAPTM4B expression with advanced tumor stage, metastasis and chemotherapy treated group in breast, ovarian, prostate and colon cancer patients. The Spearman analysis also revealed a positive linear association among HIF-1α, MDR1 and LAPTM4B in all the studied cancer patients. The elevated expression of HIF-1α, MDR1 and LAPTM4B in peripheral blood of solid tumor patients can be a predictor of metastasis, disease progression and treatment response in these cancers. However, larger studies are needed to further strengthen their role as a potential biomarker for cancer prognosis

3D-Bioprinting: A stepping stone towards enhanced medical approaches

In the past few decades, tissue engineering has been seen unprecedented escalation driving the field of artificial tissue and organ construct and brought metamorphosis in regenerative medicine. Prime advancement has been attained through the expansion of novel biomanufacturing approaches to devise and convene cells in three dimensions to fabricate tissue contrive. Accompaniment manufacturing differently known as 3D bioprinting is leading prime innovation in a number of applications in life sciences such as tissue and organ construct, personalized drug dosing, cancer model and heart tissue engineering. Overall, this review summarizes most prevalent bioprinting technologies; including laser-based bioprinting, extrusion bioprinting, injection bioprinting, stereolithography as well as biomaterial such as bioink. It also explores 3D industries, approaches such as Biomimicry, autonomous self-assembly, mini tissues and biomedical applications. Existing challenges that impede clinical mileage of bioprinting are also discussed along with future prospective.Keywords: Bioprinting, tissue engineering, tissue and organ construct, medicinal approac

Molecular characterization of circulating respiratory syncytial virus (RSV) genotypes in Gilgit Baltistan Province of Pakistan during 2011-2012 winter season.

Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract infections in young children, but very little is known about its epidemiology and circulating genotypes in Pakistan. This study analyzed the epidemiological and molecular characteristics of RSV genotypes detected in Pakistani children less than 2 years of age with acute respiratory tract infections (ARIs) in a tertiary care hospital in Gilgit Baltistan (GB) province during 2011-12 winter season. RSV was detected in 75 out of 105 children presenting with acute respiratory infection. Male infants between 2-6 months age made up the highest percentage of RSV positive cases. Epidemiological factors such as pre-maturity, mean weight, clinical features and diagnosis when compared between RSV positive and negative groups were found to be statistically insignificant. Phylogenetic analysis classified all 75 of the RSV strains into 71 strains of subgroups A and 4 strains of subgroup B, respectively. Strains belonging to subgroups A and B were further subdivided into NA1/GA2 and BA, respectively. The nucleotide and deduced amino acid sequence identities were relatively high among these strains (>90%). Both RSV-A and RSV-B isolates had two potential N-glycosylation sites in HVR2 of G protein and with heavy O-glycosylation of serine and threonine residues (G scores of 0.5-0.7). This report highlights the significance of RSV as a dominant viral etiologic agent of pediatric ARIs, and need for continued molecular epidemiological surveys for early detection of prevalent strains and newly emerging genotypes to understand epidemiology of RSV infections in various regions of Pakistan

3D-Bioprinting: A stepping stone towards enhanced medical approaches

In the past few decades, tissue engineering has been seen unprecedented escalation driving the field of artificial tissue and organ construct and brought metamorphosis in regenerative medicine. Prime advancement has been attained through the expansion of novel biomanufacturing approaches to devise and convene cells in three dimensions to fabricate tissue contrive. Accompaniment manufacturing differently known as 3D bioprinting is leading prime innovation in a number of applications in life sciences such as tissue and organ construct, personalized drug dosing, cancer model and heart tissue engineering. Overall, this review summarizes most prevalent bioprinting technologies; including laser-based bioprinting, extrusion bioprinting, injection bioprinting, stereolithography as well as biomaterial such as bioink. It also explores 3D industries, approaches such as Biomimicry, autonomous self-assembly, mini tissues and biomedical applications. Existing challenges that impede clinical mileage of bioprinting are also discussed along with future prospective

Molecular Aspects of Regional Pain Syndrome

The purpose of this review is to summarize the pathophysiology of complex regional pain syndrome (CRPS), the underlying molecular mechanisms, and potential treatment options for its management. CRPS is a multifactorial pain condition. CRPS is characterized by prolonged or excessive pain and changes in skin color and temperature, and/or swelling in the affected area, and is generally caused by stimuli that lead to tissue damage. An inflammatory response involving various cytokines and autoantibodies is generated in response to acute trauma/stress. Chronic phase pathophysiology is more complex, involving the central and peripheral nervous systems. Various genetic factors involved in the chronicity of pain have been identified in CRPS patients. As with other diseases of complex pathology, CRPS is difficult to treat and no single treatment regimen is the same for two patients. Stimulation of the vagus nerve is a promising technique being tested for different gastrointestinal and inflammatory diseases. CRPS is more frequent in individuals of 61–70 years of age with a female to male ratio of 3 : 1. Menopause, migraine, osteoporosis, and asthma all represent risk factors for CRPS and in smokers the prognosis appears to be more severe. The pathophysiological mechanisms underlying CRPS involve both inflammatory and neurological pathways. Understanding the molecular basis of CRPS is important for its diagnosis, management, and treatment. For instance, vagal nerve stimulation might have the potential for treating CRPS through the cholinergic anti-inflammatory pathway

Phylogenetic tree of the second variable region of RSV group A & B genotypes and subtypes.

<p>The prototype strain A2 and 18537 were used as the out groups in the analysis. These trees were constructed using the neighbor-joining algorithm with 1,000 bootstrap replicates using MEGA 5. The genotypes are indicated by the brackets on the right side. Only bootstrap values over 50% are displayed at the branch nodes.</p

Weekly and Monthly Distribution of RSV-positive cases from Dec 2011-March 2012.

<p>Weekly and Monthly Distribution of RSV-positive cases from Dec 2011-March 2012.</p