Current Challenges for the Effective Management of the COVID-19 Pandemic.

INTRODUCTION: Within a short period, the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) spread all over the globe and became the first pandemic of the present century. Early diagnostic tools and effective drugs are urgently needed to effectively manage the COVID-19 pandemic. Based on current literature, we provide recent updates on SARS-CoV-2 biology, available diagnostic methods, and therapeutic options for the management of COVID-19 pandemic. METHODS: A literature survey was done using Google and PubMed and Web of Science to summarize the current updates on this topic. RESULTS: Current coronavirus diagnostic tests are reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR (qRT-PCR), and reverse transcription loop-mediated isothermal amplification (RT-LAMP) which detects the presence of specific genome sequence of virus. Existing antiviral drugs or new therapeutic options such as neutralizing antibody or plasma therapy are mostly used to restrict the virus growth with a limited success. CONCLUSION: As there is no specific treatment or vaccine available to limit the infection of SARS-CoV-2, we need to rely on the existing way to limit the disease. The first priority to fight COVID-19 is development of early diagnostic tools so that infected persons can be identified and further viral transmission can be blocked. Evaluation of existing drugs or identification of new therapeutic entities becomes the major challenge to deal with the present pandemic.

Screening Laboratory Testing in Asymptomatic Minor Pediatric Blunt Trauma Leads to Unnecessary Needle Sticks.

OBJECTIVE: Screening blood work after minor injuries is common in pediatric trauma. The risk of missed injuries versus diagnostic necessity in an asymptomatic patient remains an ongoing debate. We evaluated the clinical utility of screening blood work in carefully selected asymptomatic children after minor trauma. METHODS: Patients seen at a level 1 pediatric center with "minor trauma" for blunt trauma between 2010 and 2015 were retrospectively reviewed. Exclusion criteria were age <4 of >18 years, a Glasgow Coma Scale score of <15, penetrating trauma, nonaccidental trauma, hemodynamic instability, abdominal findings (pain, distension, bruising, tenderness), hematuria, pelvic/femur fracture, multiple fractures, and operative intervention. Data abstraction included demographics, blood work, interventions, and disposition. RESULT: A total of 1308 patients were treated during the study period. Four hundred thirty-three (33%) met inclusion criteria. Mean ± SD age was 12.7 ± 4 years (range, 4-18 years), and 59% were male. Seventy-eight percent were discharged home from the emergency department. All patients had blood work. Twenty-eight percent had at least one abnormal laboratory value. The most common abnormal blood work was leukocytosis (16%). Thirty percent had an intervention, and none prompted by abnormal blood work. One patient had an intra-abdominal finding (psoas hematoma). CONCLUSION: When appropriately selected, screening laboratory testing in asymptomatic minor pediatric blunt trauma patients leads to unnecessary needle sticks without significant advantage.

Developing a Novel Ambulatory Total Parenteral Nutrition-Dependent Short Bowel Syndrome Animal Model.

BACKGROUND: Short bowel syndrome (SBS) results from extensive bowel resection. Patients with SBS require total parenteral nutrition (TPN) for survival. Understanding mechanisms contributing to TPN-associated liver injury and gut atrophy are critical in developing SBS therapies. Existing SBS models using tethered animals have significant limitations and are unlike ambulatory human SBS patients. We hypothesized that we could induce SBS in piglets and develop an ambulatory TPN-SBS model. MATERIAL AND METHODS: Eighteen neonatal pigs received duodenal and jugular catheters. They were fitted with a jacket holding TPN and a miniaturized pump. Six piglets had 90% small bowel resection and catheter placement (SBS group). Non-SBS piglets were randomized into enteral nutrition (EN) or TPN. RESULTS: Bowel resection was successfully accomplished in SBS animals. Weight gain was similar in all groups. SBS animals had increased serum bilirubin compared to EN. Mean conjugated bilirubin ± SD was 0.045 ± 0.01 for EN, (P = 0.03 EN versus TPN and P = 0.03 SBS versus EN) and 1.09 ± 1.25 for TPN, (P = 0.62 TPN versus SBS). Gut density was reduced in the TPN group compared to EN and SBS groups. Mean gut density ± SD was 0.11 ± 0.04 for TPN (P = 0.0004 TPN versus SBS and P = 0.00007 TPN versus EN) and not statistically different for EN versus SBS (P = 0.32). CONCLUSIONS: We created a novel, ambulatory TPN-SBS model using piglets, mimicking long-term TPN delivery in human SBS patients. Our model demonstrated TPN-related conjugated hyperbilirubinemia and compensatory gut hypertrophy, as noted in humans with SBS. This model holds great potential for future research.

Arabidopsis SKP1-like protein13 (ASK13) positively regulates seed germination and seedling growth under abiotic stress.

SKP1 (S-phase kinase-associated protein1) proteins are key members of the SCF (SKP-cullin-F-box protein) E3 ligase complexes that ubiquitinate target proteins and play diverse roles in plant biology. However, in comparison with other members of the SCF complex, knowledge of SKP1-like proteins is very limited in plants. In the present work, we report that Arabidopsis SKP1-like protein13 (ASK13) is differentially regulated in different organs during seed development and germination and is up-regulated in response to abiotic stress. Yeast two-hybrid library screening and subsequent assessment of in vivo interactions through bimolecular fluorescence complementation analysis revealed that ASK13 not only interacts with F-box proteins but also with other proteins that are not components of SCF complexes. Biochemical analysis demonstrated that ASK13 not only exists as a monomer but also as a homo-oligomer or heteromer with other ASK proteins. Functional analysis using ASK13 overexpression and knockdown lines showed that ASK13 positively influences seed germination and seedling growth, particularly under abiotic stress. Taken together, our data strongly suggest that apart from participation to form SCF complexes, ASK13 interacts with several other proteins and is implicated in different cellular processes distinct from protein degradation.

Laparoscopic-assisted divided colostomy for anorectal malformation case series: a description of technique, clinical outcomes and a review of the literature.

OBJECTIVE: To present a case series of pediatric patients who underwent a laparoscopic-assisted divided colostomy for anorectal malformations, describe our technique, and provide a review of the literature on laparoscopic-assisted colostomy in pediatric patients. METHODS: We performed a retrospective review of six patients born with anorectal malformations, who received a laparoscopic-assisted colostomy from 2012 to 2016 at Cardinal Glennon Children's Medical Center. RESULTS: The average operating time was 74.5 min. Laparoscopic colostomy types included divided (n = 5) and end colostomy with Hartmann's (n = 1). Location of the colostomy was selected just distal to the descending colon (n = 5) or at the sigmoid flexure (n = 1). Feeds and stoma production was achieved within 24 h from surgery in most patients. There were no major complications except one patient having a mucosal fistula prolapse that was easily reduced. CONCLUSIONS: Laparoscopic-assisted colostomy in the management of anorectal malformations is a safe and effective technique. It offers similar advantages of the open technique, with the added benefits of avoiding wound-related complications and improved cosmetic results.

Optimal timing of cholecystectomy in children with gallstone pancreatitis.

BACKGROUND: Little data exist regarding the recurrence of pancreatitis in pediatric patients with gallstone pancreatitis awaiting cholecystectomy. This study evaluates the recurrence rate of pancreatitis after acute gallstone pancreatitis based on the timing of cholecystectomy in pediatric patients. MATERIALS AND METHODS: A retrospective chart review of all patients admitted with gallstone pancreatitis from 2007 to 2015 was performed. Children were divided into the following five groups. Group 1 had surgery during the index admission. Group 2 had surgery within 2 wk of discharge. Group 3 had surgery between 2 and 6 wk postdischarge. Group 4 had surgery 6 wk after discharge, and group 5 patients had no surgery. The recurrence rates of pancreatitis were calculated for all groups. RESULTS: Forty-eight patients with gallstone pancreatitis were identified in this study. The 19 patients in group 1 had no recurrence of their pancreatitis. Of the remaining 29 patients, nine (31%) had recurrence of pancreatitis or required readmission for abdominal pain prior to their cholecystectomy. In group 2, two of the eight patients (25%) had recurrent pancreatitis. In group 3, three of eight patients (37.5%) developed recurrent pancreatitis. In group 4, three of five patients (60%), and in group 5, one of eight. No children in group 5 had demonstrable gallstones at presentation, only sludge in their gallbladder. CONCLUSIONS: Cholecystectomy during the index admission is associated with no recurrence or readmission for pancreatitis. Therefore, we recommend that cholecystectomy be performed after resolution of an episode of gallstone pancreatitis during index admission.

Rice PROTEIN l-ISOASPARTYL METHYLTRANSFERASE isoforms differentially accumulate during seed maturation to restrict deleterious isoAsp and reactive oxygen species accumulation and are implicated in seed vigor and longevity.

PROTEIN l-ISOASPARTYL O-METHYLTRANSFERASE (PIMT) is a protein-repairing enzyme involved in seed vigor and longevity. However, the regulation of PIMT isoforms during seed development and the mechanism of PIMT-mediated improvement of seed vigor and longevity are largely unknown. In this study in rice (Oryza sativa), we demonstrate the dynamics and correlation of isoaspartyl (isoAsp)-repairing demands and PIMT activity, and their implications, during seed development, germination and aging, through biochemical, molecular and genetic studies. Molecular and biochemical analyses revealed that rice possesses various biochemically active and inactive PIMT isoforms. Transcript and western blot analyses clearly showed the seed development stage and tissue-specific accumulation of active isoforms. Immunolocalization studies revealed distinct isoform expression in embryo and aleurone layers. Further analyses of transgenic lines for each OsPIMT isoform revealed a clear role in the restriction of deleterious isoAsp and age-induced reactive oxygen species (ROS) accumulation to improve seed vigor and longevity. Collectively, our data suggest that a PIMT-mediated, protein repair mechanism is initiated during seed development in rice, with each isoform playing a distinct, yet coordinated, role. Our results also raise the intriguing possibility that PIMT repairs antioxidative enzymes and proteins which restrict ROS accumulation, lipid peroxidation, etc. in seed, particularly during aging, thus contributing to seed vigor and longevity.

High resolution 4D HPCH experiment for sequential assignment of (13)C-labeled RNAs via phosphodiester backbone.

The three-dimensional structure determination of RNAs by NMR spectroscopy requires sequential resonance assignment, often hampered by assignment ambiguities and limited dispersion of (1)H and (13)C chemical shifts, especially of C4'/H4'. Here we present a novel through-bond 4D HPCH NMR experiment involving phosphate backbone where C4'-H4' correlations are resolved along the (1)H3'-(31)P spectral planes. The experiment provides high peak resolution and effectively removes ambiguities encountered during assignments. Enhanced peak dispersion is provided by the inclusion of additional (31)P and (1)H3' dimensions and constant-time evolution of chemical shifts. High spectral resolution is obtained by using non-uniform sampling in three indirect dimensions. The experiment fully utilizes the isotopic (13)C-labeling with evolution of C4' carbons. Band selective (13)C inversion pulses are used to achieve selectivity and prevent signal dephasing due to the C4'-C3' and C4'-C5' homonuclear couplings. Multiple quantum line narrowing is employed to minimize sensitivity loses. The 4D HPCH experiment is verified and successfully applied to a non-coding 34-nt RNA consisting typical structure elements and a 14-nt RNA hairpin capped by cUUCGg tetraloop.

C4'/H4' selective, non-uniformly sampled 4D HC(P)CH experiment for sequential assignments of (13)C-labeled RNAs.

A through bond, C4'/H4' selective, "out and stay" type 4D HC(P)CH experiment is introduced which provides sequential connectivity via H4'(i)-C4'(i)-C4'(i-1)-H4'(i-1) correlations. The (31)P dimension (used in the conventional 3D HCP experiment) is replaced with evolution of better dispersed C4' dimension. The experiment fully utilizes (13)C-labeling of RNA by inclusion of two C4' evolution periods. An additional evolution of H4' is included to further enhance peak resolution. Band selective (13)C inversion pulses are used to achieve selectivity and prevent signal dephasing due to the of C4'-C3' and C4'-C5' homonuclear couplings. For reasonable resolution, non-uniform sampling is employed in all indirect dimensions. To reduce sensitivity losses, multiple quantum coherences are preserved during shared-time evolution and coherence transfer delays. In the experiment the intra-nucleotide peaks are suppressed whereas inter-nucleotide peaks are enhanced to reduce the ambiguities. The performance of the experiment is verified on a fully (13)C, (15)N-labeled 34-nt hairpin RNA comprising typical structure elements.

PROTEIN L-ISOASPARTYL METHYLTRANSFERASE2 is differentially expressed in chickpea and enhances seed vigor and longevity by reducing abnormal isoaspartyl accumulation predominantly in seed nuclear proteins.

PROTEIN l-ISOASPARTYL METHYLTRANSFERASE (PIMT) is a widely distributed protein-repairing enzyme that catalyzes the conversion of abnormal l-isoaspartyl residues in spontaneously damaged proteins to normal aspartyl residues. This enzyme is encoded by two divergent genes (PIMT1 and PIMT2) in plants, unlike many other organisms. While the biological role of PIMT1 has been elucidated, the role and significance of the PIMT2 gene in plants is not well defined. Here, we isolated the PIMT2 gene (CaPIMT2) from chickpea (Cicer arietinum), which exhibits a significant increase in isoaspartyl residues in seed proteins coupled with reduced germination vigor under artificial aging conditions. The CaPIMT2 gene is found to be highly divergent and encodes two possible isoforms (CaPIMT2 and CaPIMT2') differing by two amino acids in the region I catalytic domain through alternative splicing. Unlike CaPIMT1, both isoforms possess a unique 56-amino acid amino terminus and exhibit similar yet distinct enzymatic properties. Expression analysis revealed that CaPIMT2 is differentially regulated by stresses and abscisic acid. Confocal visualization of stably expressed green fluorescent protein-fused PIMT proteins and cell fractionation-immunoblot analysis revealed that apart from the plasma membrane, both CaPIMT2 isoforms localize predominantly in the nucleus, while CaPIMT1 localizes in the cytosol. Remarkably, CaPIMT2 enhances seed vigor and longevity by repairing abnormal isoaspartyl residues predominantly in nuclear proteins upon seed-specific expression in Arabidopsis (Arabidopsis thaliana), while CaPIMT1 enhances seed vigor and longevity by repairing such abnormal proteins mainly in the cytosolic fraction. Together, our data suggest that CaPIMT2 has most likely evolved through gene duplication, followed by subfunctionalization to specialize in repairing the nuclear proteome.

Selective diagonal-free (13)C, (13)C-edited aliphatic-aromatic NOESY experiment with non-uniform sampling.

A band-selective aromatic-aliphatic C,C-edited four-dimensional NOESY experiment is proposed here. Its key advantage is the absence of auto-correlation signals which makes it very attractive for joint use with non-uniform sampling. It is demonstrated here that the sensitivity of the experiment is not significantly affected by utilization of selective pulses (for either aromatic-13C or aliphatic-13C spins). The method was applied to the sample of E32Q mutant of human S100A1 protein, a homodimer of total molecular mass ~20 kDa. High-resolution 4D spectra were obtained from ~1.5 % of sampling points required conventionally. It is shown that superior resolution facilitates unambiguous assignment of observed aliphatic-aromatic cross-peaks. Additionally, the addition of aliphatic-13C dimension enables to resolve peaks with degenerated aliphatic (1)H chemical shifts. All observed cross-peaks were validated against previously determined 3D structure of E32Q mutant of S100A1 protein (PDB 2LHL). The increased reliability of structural constraints obtained from the proposed high-resolution 4D 13C(ali),13C(aro)-edited NOESY can be exploited in the automated protocols of structure determination of proteins.

Ectopic expression of the ABA-inducible dehydration-responsive chickpea L-myo-inositol 1-phosphate synthase 2 (CaMIPS2) in Arabidopsis enhances tolerance to salinity and dehydration stress.

Myo-inositol participates in many different aspects of plant physiology and myo-inositol 1-phosphate synthase (MIPS; EC 5.5.1.4) catalyzes the rate limiting step of inositol biosynthetic pathway. Chickpea (Cicer arietinum), a drought-tolerant leguminous crop plant, is known to accumulate increased inositol during dehydration stress. Previously, we reported two differentially expressed divergent genes (CaMIPS1 and CaMIPS2) encoding two MIPS isoforms in chickpea. In this communication, we demonstrated that CaMIPS2 is an early dehydration-responsive gene and is also rapidly induced by exogenous ABA application, while CaMIPS1 expression is not much influenced by dehydration or ABA. The regulation of expression of these two genes has been studied by examining their promoter activity through GUS reporter gene and differential promoter activity has been observed. Moreover, unlike CaMIPS1 promoter, CaMIPS2 promoter contains CRT/DRE cis-regulatory element which seems to play a key role in dehydration-induced expression of CaMIPS2. Furthermore, CaMIPS1 and CaMIPS2 have been successfully complemented and shown to repair the defect of seedling growth and altered seed phenotype of Atmips1 mutant. Moreover, Arabidopsis transgenic plants overexpressing CaMIPS1 or CaMIPS2 exhibit improved tolerance to salinity and dehydration stresses and such tolerance of transgenic plants is correlated with their elevated level of inositol. Remarkably, CaMIPS2 transgenic lines perform better in all attributes than CaMIPS1 transformants under such stress conditions, due to comparatively unabated production of inositol by CaMIPS2 enzyme, as this enzyme retains significant activity under stress conditions.

Differentially expressed myo-inositol monophosphatase gene (CaIMP) in chickpea (Cicer arietinum L.) encodes a lithium-sensitive phosphatase enzyme with broad substrate specificity and improves seed germination and seedling growth under abiotic stresses.

myo-Inositol monophosphatase (IMP) is an essential enzyme in the myo-inositol metabolic pathway where it primarily dephosphorylates myo-inositol 1-phosphate to maintain the cellular inositol pool which is important for many metabolic and signalling pathways in plants. The stress-induced increased accumulation of inositol has been reported in a few plants including chickpea; however, the role and regulation of IMP is not well defined in response to stress. In this work, it has been shown that IMP activity is distributed in all organs in chickpea and was noticeably enhanced during environmental stresses. Subsequently, using degenerate oligonucleotides and RACE strategy, a full-length IMP cDNA (CaIMP) was cloned and sequenced. Biochemical study revealed that CaIMP encodes a lithium-sensitive phosphatase enzyme with broad substrate specificity, although maximum activity was observed with the myo-inositol 1-phosphate and l-galactose 1-phosphate substrates. Transcript analysis revealed that CaIMP is differentially expressed and regulated in different organs, stresses and phytohormones. Complementation analysis in Arabidopsis further confirmed the role of CaIMP in l-galactose 1-phosphate and myo-inositol 1-phosphate hydrolysis and its participation in myo-inositol and ascorbate biosynthesis. Moreover, Arabidopsis transgenic plants over-expressing CaIMP exhibited improved tolerance to stress during seed germination and seedling growth, while the VTC4/IMP loss-of-function mutants exhibited sensitivity to stress. Collectively, CaIMP links various metabolic pathways and plays an important role in improving seed germination and seedling growth, particularly under stressful environments.

Cloning, expression and functional validation of drought inducible ascorbate peroxidase (Ec-apx1) from Eleusine coracana.

Eleusine coracana (finger millet) is a stress-hardy but under-utilized cereal crop that possesses an efficient antioxidant defense system. The plant is capable of enduring long durations of water deficit stress. Experiments were conducted to clone a potent stress responsive isoform of ascorbate peroxidase and validate its role under drought stress. Reverse transcriptase PCR was used to obtain the partial cDNA of apx1 gene, from a meticulously screened drought tolerant genotype of E. coracana (PR202). Using RACE strategy, the full length apx1 cDNA was cloned and sequenced. The cDNA length of the E. coracana apx1 (Ec-apx1) gene is 1,047 bp with a 750 bp ORF, encoding a 250 amino acid protein having a molecular weight of 28.5 kDa. The identity of the amino acid sequence, deduced from the cDNA, with the APX family homologs was about 74-97 %. The full-length apx1 ORF was sub-cloned in a prokaryotic expression vector pET23b. The recombinant fusion protein, Ec-apx1, had high expression level in BL21 strain of E. coli and exhibited APX enzyme activity. The structure-function relationship of the protein was deduced by modelling a three-dimensional structure of Ec-apx1, on the basis of comparative homology using SWISS-MODEL. Real time PCR analysis of Ec-apx1 expression at mRNA level showed that the transcript increased under drought stress, with maximum levels attained 5-days after imposition of stress. Our results suggest that Ec-apx1 has a distinct pattern of expression and plays a pivotal role in drought stress tolerance. Therefore, the cloned isoform of ascorbate peroxidase can be used for developing stress tolerant genotypes of important crops, through transgenic approach.

Probing local backbone geometries in intrinsically disordered proteins by cross-correlated NMR relaxation.

An ultra-high-resolution NMR experiment for the measurement of intraresidue (1)H(i)-(15)N(i)-(13)C'(i) dipolar-chemical shift anisotropy relaxation interference is employed to extract information about local backbone geometries in intrinsically disordered proteins. The study of tumor suppressor BASP1 revealed a population shift of ß-turn geometries at low pH conditions and a compaction of the BASP1 structural ensemble.

Comparative Study of the Management of Distal Tibia Fractures by Nailing Versus Plating.

Introduction The purpose of this study was to evaluate the management of distal tibial fractures treated by interlocking nail and plate osteosynthesis and to assess their functional outcome according to the American Orthopaedic Foot and Ankle Society (AOFAS) score and complications. Methods Twenty patients were operated on in each group, i.e., intramedullary nailing (IMN) and plating (minimally invasive plate osteosynthesis, MIPO). The patients were regularly followed up at six weeks, 12 weeks, six months, and one year and evaluated clinically and radiologically with respect to operating time, union time, and functional outcome on the basis of AOFAS score and complications. Results The mean union time for the IMN group was 18.45±2.45 weeks and for the MIPO group was 20±3.21 weeks (p-value >0.05). The mean AOFAS score in the MIPO group was 91.2±6.81 and in the IMN group was 92.6±5.41 (p-value >0.05). Lesser complications in terms of implant irritation, ankle stiffness, and infection were observed in the IMN group than in the MIPO group (p-value <0.05). Conclusion Both the IMN and MIPO groups had satisfactory outcomes for treating distal tibial fractures, with a higher risk of wound complications in the MIPO group.

Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride.

High altitude/hypoxia training is known to improve physical performance in athletes. Hypoxia induces hypoxia inducible factor-1 (HIF-1) and its downstream genes that facilitate hypoxia adaptation in muscle to increase physical performance. Cobalt chloride (CoCl2), a hypoxia mimetic, stabilizes HIF-1, which otherwise is degraded in normoxic conditions. We studied the effects of hypoxia preconditioning by CoCl2 supplementation on physical performance, glucose metabolism, and mitochondrial biogenesis using rodent model. The results showed significant increase in physical performance in cobalt supplemented rats without (two times) or with training (3.3 times) as compared to control animals. CoCl2 supplementation in rats augmented the biological activities of enzymes of TCA cycle, glycolysis and cytochrome c oxidase (COX); and increased the expression of glucose transporter-1 (Glut-1) in muscle showing increased glucose metabolism by aerobic respiration. There was also an increase in mitochondrial biogenesis in skeletal muscle observed by increased mRNA expressions of mitochondrial biogenesis markers which was further confirmed by electron microscopy. Moreover, nitric oxide production increased in skeletal muscle in cobalt supplemented rats, which seems to be the major reason for peroxisome proliferator activated receptor-gamma coactivator-1α (PGC-1α) induction and mitochondrial biogenesis. Thus, in conclusion, we state that hypoxia preconditioning by CoCl2 supplementation in rats increases mitochondrial biogenesis, glucose uptake and metabolism by aerobic respiration in skeletal muscle, which leads to increased physical performance. The significance of this study lies in understanding the molecular mechanism of hypoxia adaptation and improvement of work performance in normal as well as extreme conditions like hypoxia via hypoxia preconditioning.

Identification of haptoglobin and apolipoprotein A-I as biomarkers for high altitude pulmonary edema.

We have investigated the plasma proteome using 2D gel electrophoresis and matrix-assisted laser desorption/ionization tandem time of flight from patients with high altitude pulmonary edema (HAPE). A complete proteomic analysis was performed on 20 patients with HAPE and ten healthy sea level controls. In total, we have identified 25 protein spots in human plasma and found that 14 of them showed altered changes in HAPE patients, which mainly were acute phase proteins (APPs), compliment components, and apolipoproteins among others. Among the APPs, haptoglobin α2 chain, haptoglobin ß chain, transthyretin, and plasma retinol binding precursor showed overexpression in HAPE patients as compared to controls. To validate the result of proteomic analysis, two proteins were selected for enzyme-linked immunosorbent assay and Western blotting analysis. Our data conclusively shows that two proteins, haptoglobin and apolipoprotein A-I are upregulated in plasma of HAPE patients. These proteins may provide a fast and effective control of inflammatory damage until the subsequent mechanisms can begin to operate. Taken together, our findings further support the hypothesis that inflammatory response system is linked to the pathophysiology of HAPE.

Responses to drought induced oxidative stress in five finger millet varieties differing in their geographical distribution.

The study presents the impact of drought stress on five finger millet varieties (PR202, VL146, VL315, PES400 and VR708), representing contrasting areas of Indian sub-continent. Drought stress induced increase in the activity of superoxide dismutase, ascorbate peroxidase and glutathione reductase was higher in PR202 and VL315, while the activity was lower in the varieties PES400 and VR708. Ascorbate peroxidase : superoxide dismutase ratio, which is a crucial factor in alleviating drought stress, was higher in varieties PR202 and VL315, whilst the varieties PES400 and VR708 exhibited a lower ratio under stress. The variety PES400 recorded maximum stress induced damage, as indicated by higher accumulation of malondialdehyde and hydrogen peroxide; whereas the variety PR202 recorded least stress induced cytotoxic damage. The results clearly indicate that better drought tolerance of the variety PR202 is positively related to the capacity of its antioxidant system to scavenge reactive oxygen species, resulting in a reduced incidence of oxidative damage. Ascorbate peroxidase : superoxide dismutase ratio is found to be a critical factor governing the stress tolerance potential of different varieties. Therefore, varieties PR202 and VL315 were found to be tolerant while PES400 was susceptible to drought stress.

Pharmacotherapy to gene editing: potential therapeutic approaches for Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS), commonly called progeria, is an extremely rare disorder that affects only one child per four million births. It is characterized by accelerated aging in affected individuals leading to premature death at an average age of 14.5 years due to cardiovascular complications. The main cause of HGPS is a sporadic autosomal dominant point mutation in LMNA gene resulting in differently spliced lamin A protein known as progerin. Accumulation of progerin under nuclear lamina and activation of its downstream effectors cause perturbation in cellular morphology and physiology which leads to a systemic disorder that mainly impairs the cardiovascular system, bones, skin, and overall growth. Till now, no cure has been found for this catastrophic disorder; however, several therapeutic strategies are under development. The current review focuses on the overall progress in the field of therapeutic approaches for the management/cure of HGPS. We have also discussed the new disease models that have been developed for the study of this rare disorder. Moreover, we have highlighted the therapeutic application of extracellular vesicles derived from stem cells against aging and aging-related disorders and, therefore, suggest the same for the treatment of HGPS.