Bacteriophage therapy- a refurbished age-old potential strategy to treat antibiotic and multidrug resistant bacterial infections in future.

The worldwide prevalence of antimicrobial resistance coupled with the unavailability of newer antibiotics, has brought the sharp focus back among the scientific community, towards the discovery of novel alternative therapeutics to tackle the menace. Consequently, in the current post-antibiotic era, 'Bacteriophage Therapy' has emerged as one of the most promising option to address this problem. Bacteriophages, actually discovered long back, has shown greater potential to kill various bacterial pathogens, including the resistant clinical ones. Some of the other advantages for the use of bacteriophage therapy to treat infectious diseases include, wider availability of these microorganisms in nature, host-specific action, absence of any significant side-effects in humans and most often also exhibiting a broader anti-bacterial potential. In the recent times, the potential of phage therapy has been demonstrated in various treatments, clinical trials and infection models across the globe, where even antibiotics have completely failed. To address the global threat of AMR, WHO and UN have jointly illustrated "One Health" approach, recently extending the context to bacteriophage therapy. Many pharmaceutical companies have also recently started employing bacteriophages for developing different kinds of formulations for catering to medical and other industries. It has even shown great effect as combinatorial therapy along with antibiotics, to treat or manage various critical antibiotic resistant clinical infections. This continuously expanding potential of the bacteriophages holds great promise in the future, in the fight against the rising threat of AMR globally.

Alpha-induced production and robust radiochemical separation of 43Sc as an emerging radiometal for formulation of PET radiopharmaceuticals.

Scandium-43 is an emerging PET radiometal that was produced by α-particle bombardment on natural CaCO3 target via natCa (α,p) 43Sc and natCa (α,n) 43Ti→43Sc reactions using K-130 cyclotron at VECC. A robust radiochemical procedure based on selective precipitation of 43Sc as Sc(OH)3 was developed for separation of the radioisotope from the irradiated target. The overall yield of the separation process was >85% and it was obtained in a form suitable for preparation of target specific radiopharmaceuticals for PET imaging of cancer.

Role of vitamin D in targeting cancer and cancer stem cell populations and its therapeutic implications.

Cancer is recognized globally as the second-most dominating and leading cause of morbidities. Fighting the global health epidemic threat posed by cancer requires progress and improvements in imaging techniques, surgical techniques, radiotherapy, and chemotherapy. The existence of a small subpopulation of undifferentiated cells known as cancer stem cells has been supported by accumulating evidence and ongoing research. According to clinical data, cancer recurrence, tumor development, and metastasis are thought to be caused by CSCs. Nutritional or dietary supplements can help you to fight against cancer and cope with the treatment side effects. Vitamin D, sometimes known as the sunshine vitamin, is produced in the skin in reaction to sunlight. Vitamin D deficiency is hazardous to any degree, increasing the risk of diseases such as cancer and disorders like osteoporosis. Bioactive vitamin D, or calcitriol, regulates several biological pathways. Many modes of action of Vitamin D might be helpful in protecting somatic stem cells (e.g., DNA damage repair and oxidative stress protection) or restricting cancer stem cell growth (e.g., cell cycle arrest, cell apoptosis). Researchers have recently begun to investigate the inhibitory effects of dietary vitamin D on cancer stem cells. In this review, we investigated the therapeutic impact of vitamin D and its molecular processes to target cancer and cancer stem cells as well.

Combination therapy of Tocilizumab and steroid for management of COVID-19 associated cytokine release syndrome: A single center experience from Pune, Western India.

ABSTRACT: Cytokine release syndrome (CRS) or cytokine storm is thought to be the cause of inflammatory lung damage, worsening pneumonia and death in patients with COVID-19. Steroids (Methylprednislone or Dexamethasone) and Tocilizumab (TCZ), an interleukin-6 receptor antagonist, are approved for treatment of CRS in India. The aim of this study was to evaluate the efficacy and safety of combination therapy of TCZ and steroid in COVID-19 associated CRS.This retrospective cohort study was conducted at Noble hospital and Research Centre (NHRC), Pune, India between April 2 and November 2, 2020. All patients administered TCZ and steroids during this period were included. The primary endpoint was incidence of all cause mortality. Secondary outcomes studied were need for mechanical ventilation and incidence of systemic and infectious complications. Baseline and time dependent risk factors significantly associated with death were identified by Relative risk estimation.Out of 2831 admitted patients, 515 (24.3% females) were administered TCZ and steroids. There were 135 deaths (26.2%), while 380 patients (73.8%) had clinical improvement. Mechanical ventilation was required in 242 (47%) patients. Of these, 44.2% (107/242) recovered and were weaned off the ventilator. Thirty seven percent patients were managed in wards and did not need intensive care unit (ICU) admission. Infectious complications like hospital acquired pneumonia, blood stream bacterial and fungal infections were observed in 2.13%, 2.13% and 0.06% patients respectively. Age ≥ 60 years (P = .014), presence of co-morbidities like hypertension (P = .011), IL-6 ≥ 100 pg/ml (P = .002), D-dimer ≥ 1000 ng/ml (P < .0001), CT severity index ≥ 18 (P < .0001) and systemic complications like lung fibrosis (P = .019), cardiac arrhythmia (P < .0001), hypotension (P < .0001) and encephalopathy (P < .0001) were associated with increased risk of death.Combination therapy of TCZ and steroids is likely to be safe and effective in management of COVID-19 associated cytokine release syndrome. Efficacy of this anti-inflammatory combination therapy needs to be validated in randomized controlled trials.

Radioactive ion beams of 111In using ECR plasma sputtering method.

Radioactive ion beams of 111In (indium-111, half-life 2.8 days) have been produced using the plasma sputtering method in an electron cyclotron resonance (ECR) ion source at the Variable Energy Cyclotron Centre RIB facility. Indium isotopes were first produced by bombarding a natural silver target with a 32 MeV, 40 µA alpha particle beam from the K-130 cyclotron. After radio-chemical separation, about 25 mCi In-chloride was deposited on an aluminum electrode and inserted in the plasma chamber of the ECR. Indium ions produced by ion induced sputtering in the plasma were extracted from the ion source, isotopically separated, and a pure 111In beam was measured at the focal plane of the separator. The measured 111In beam intensity was 2.67 × 105 particles/s for a beam energy of 5 keV.

Renal cell carcinoma and plasma cell myeloma: Unique association and clinical implications.

Several case series, in the recent past, have postulated an association between plasma cell myeloma (MM) and renal cell carcinoma (RCC). Population-based data have revealed a bi-directional association between these two malignancies, which points to shared risk factors, similar cytokine (Interleukin-6, IL-6) requirements for growth and survival, and overlapping clinical presentation. The presence of lytic lesions in a patient with prior RCC may simulate bone metastasis; thus, leading to a diagnostic pitfall with potentially adverse clinical implications. Besides these, therapeutic strategies employed for MM have been tried for RCCs with partial success. We aimed to describe two patients, aged 64 and 54 years, with RCC-MM association, with review of relevant literature; and create awareness among pathologists/hematologists, and oncologists. Elucidating a common genetic basis might throw some light in understanding the pathobiology of these tumors and development of newer targeted therapies.

Isolation and characterization of a nodavirus associated with mass mortality in Asian seabass (Lates calcarifer) from the west coast of India.

A fish nodavirus was detected in the juveniles of Asian seabass (Lates calcarifer) during a massive outbreak in the seabass cage culture farm located in the south west coast of India. The clinical signs of the disease included anorexia, inflated abdomen, exophthalmia, darkening of the whole body, erratic swimming and cork-screw type movement followed by death. The dead and the moribund fish were analyzed for nodavirus by reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primers targeting the T4 region of RNA2 coat protein gene. This is the first report of nodavirus infection in the fresh water cage-reared seabass fish in the west coast of India. The piscine nodavirus was detected in the brain, retina and kidney of all the fishes examined. The PCR products were cloned and sequenced. The sequence analysis showed more than 90 % homology with the other coat protein gene sequence of piscine nodaviruses from other countries. The phylogenetic analysis based on the partial nucleotide sequence of RNA2 coat protein gene revealed that the virus belonged to the red-spotted grouper nervous necrosis virus, which is one of the widely distributed genotype among the other four known genotypes of piscine nodavirus.

F-cell levels are altered with erythrocyte density in sickle cell disease.

Lighter cells from density fractionated erythrocytes of sickle cell disease (SCD) patients carry higher amount of externalized phosphatidylserine (PS) and cell surface glycophorins compared to the denser counterparts. Further analysis also revealed that the denser cells contained higher levels of fetal hemoglobin (HbF) compared to the lighter cells, supported by the presence of larger number of F-cells in these populations. In this report, we have found direct evidence on the higher survival of the HbF rich erythrocytes in SCD.

Differential regulation of redox proteins and chaperones in HbEß-thalassemia erythrocyte proteome.

PURPOSE: In (hemoglobin, Hb) HbEß-thalassemia, HbE (ß-26 Glu→Lys) interacts with ß-thalassemia to produce clinical manifestation of varying severity. This is the first proteomic effort to study changes in protein levels of erythrocytes isolated from HbEß-thalassemic patients compared to normal. EXPERIMENTAL DESIGN: We have used 2-DE and MALDI-MS/MS-based techniques to investigate the differential proteome profiling of membrane and Hb-depleted fraction of cytosolic proteins of erythrocytes isolated from the peripheral blood samples of HbEß-thalassemia patients and normal volunteers. RESULTS: Our study showed that redox regulators such as peroxiredoxin 2, Cu-Zn superoxide dismutase and thioredoxin and chaperones such as α-hemoglobin stabilizing protein and HSP-70 were upregulated in HbEß-thalassemia. We have also observed larger amounts of membrane associated globin chains and indications of disruption of spectrin-based junctional complex in the membrane skeleton of HbEß-thalassemic erythrocytes upon detection of low molecular weight fragments of ß-spectrin and decrease in ß-actin and dematin content. CONCLUSION AND CLINICAL RELEVANCE: We have observed interesting changes in the proteomic levels of redox regulators and chaperons in the thalassemic hemolysates and have observed strong correlation or association of the extent of such proteomic changes with HbE levels. This could be important in understanding the role of HbE in disease progression and pathophysiology.

Fluorimetric study of interaction of merbromin with trypsin.

Interaction of merbromin with trypsin is of bovine origin has been studied by monitoring the absorption steady-state and time-resolved fluorescence spectral properties of the dye. Studies have been done in media of varying pH at different trypsin concentrations. It has been observed that trypsin brings about a quenching of fluorescence of the dye. The quenching is static in nature and the equilibrium constant of dye-trypsin interaction in the ground-state has been determined from quenching studies. Steady-state anisotropy of the dye increases in presence of trypsin in the medium. Values of micro-viscosity in the vicinity of the fluorophore in media containing trypsin have been determined from measurements of fluorescence anisotropy. Time-resolved fluorescence studies indicate the existence of two decaying states for the dye. The fractional contribution to the time-resolved decay changes with pH. The average lifetime, however, does not depend on the concentration of trypsin.

Spectroscopic study of association of a hemicyanine dye in mixed aqueous binary solvents.

Electronic absorption and steady state emission properties of a hemicyanine dye [4-[4-(dimethylamino)styryl]-1-docosylpyridinium bromide], have been studied in several pure solvents and two mixed binary solvents (water+ethanol and water+acetonitrile). In pure solvents the band-width of the absorption spectrum correlates well with the Stoke's shift. In mixed aqueous solvents two different molecular forms of the solute, viz. the monomer and the dimer of the solute exists in equilibrium. Thermodynamic parameters (e.g. the Delta G degrees and Delta H degrees ) characterizing the equilibrium have been determined. While the value of Delta G degrees changes very slightly with the composition of the binary mixture, the value of Delta H degrees has been observed to depend significantly with solvent composition.

Enhanced oxidative cross-linking of hemoglobin E with spectrin and loss of erythrocyte membrane asymmetry in hemoglobin Ebeta-thalassemia.

Oxidative stress to the erythrocytes is associated with formation of large molecular complexes of hemoglobin and the skeletal protein, spectrin. In this work, such complexes are formed with hemoglobin mixtures isolated from patients suffering from HbEbeta-thalassemia with elevated levels of the HbE and purified erythroid spectrin in the presence of hydrogen peroxide. The complexes are separated on 4% SDS-PAGE and analyzed by densitometry. The results indicate enhanced formation of complexes with higher amounts of HbE, the most common hemoglobin variant prevalent in Southeast Asia. The binding affinity of spectrin with hemoglobin, in the absence of hydrogen peroxide, was found to increase with hemoglobin mixtures enriched with HbE. The presence of ATP was also found to decrease the overall yield of such complexes. Flow cytometric measurements of phosphatidylserine on the red cell surface also showed a lower degree of membrane asymmetry in HbEbeta-thalassemic patients than in normal subjects. The present work shows enhanced formation of high molecular weight cross-linked complexes of hemoglobin derivatives with erythroid spectrin in HbEbeta-thalassemia.