Artificial Photosynthesis an Alternative Source of Renewable Energy: Potential and Limitations

Artificial photosynthesis system (APS) uses biomimetic systems to duplicate the process of natural photosynthesis that utilizes copious resources of water, carbon dioxide and sunlight to produce oxygen and energy-rich compounds and has potential to be an alternative source of renewable energy. APS like natural photosynthesis includes the splitting of water into oxygen and hydrogen, and the reduction of carbon dioxide into various hydrocarbons such as formic acid (HCOOH), methane (CH4) and carbon monoxide (CO), or even pure hydrogen fuel. These processes are accomplished by a handful of device designs, including photoelectrochemical cells or photovoltaic-coupled electrolyzers which are driven by energy extracted from sunlight photons as well as suitable catalysts. Researchers are trying to combine advantageous components from both natural photosynthesis and artificial photosynthesis to create a semi-artificial photosynthesis system, involving the incorporation of enzymes or even whole-cell into synthetic devices. However, there are several limitations to the advancement of this field which are mainly centered on the inability to establish a system that is cost-effective, long-term durable and has the highest efficiency. Artificial photosynthesis devices can also function as atmospheric cleansers by extracting the excess amount of carbon dioxide and releasing back oxygen into the environment. Although there is still a long way to go to empower society with energy supplied through artificial photosynthesis, at the same time it is both desirable and necessary. To date, the efforts to commercialize APS have been fruitful, and it will soon be a viable alternative fuel source

Downmodulation of lysophosphatidic acid by Berberine loaded folate-conjugated glycol chitosan nanoparticles (BFGCN) to mitigate Rheumatoid arthritis (RA) & Cardio-vascular disease(CVD): Current knowledge and future perspectives

440-449The perils of cardiovascular diseases (CVD) are enhanced by systemic chronic inflammation in autoimmune disorders like Rheumatoid arthritis (RA), in which the patients generally exhibit a high inflammatory burden, dyslipidemia causing 50-60% of RA patients susceptible to CVD dependent mortality. Lysophosphatidic acid (LPA) is a polar, pleiotropic lipid molecule that is water soluble and present in the synovial fluid that can be exploited as an effective biomarker for lipid-signalling. Current research on alternative medicine has recognized various new molecular targets of Berberine (BBR) and established novel signals in support of the efficacy and therapeutic potential of BBR to fight CVD. Therefore, BBR, an alkaloid with poor aqueous solubility could be foreseen as a therapeutic strategy for the reduction of inflammation induced lipidemia by targeting the macrophages and modulating their functions. Hence, a novel BBR loaded folate-conjugated glycol chitosan nanoparticles (BFGCN) could be hypothesized as a three-pronged approach to target activated macrophages, fibroblasts of synovial fluid for downmodulation of LPA. The greatest challenge is the heterogeneity, complexity and interdependence of RA and CVD. Investigation of prognostic and predictive biomarkers is urgently required. Therefore, an improved understanding of the pathogenesis of RA would facilitate identifying an improved targeted treatment and management of RA patients

Smart Drug-Delivery Systems in the Treatment of Rheumatoid Arthritis: Current, Future Perspectives

Rheumatoid arthritis (RA) is a progressive autoimmune inflammatory disorder characterized by cellular infiltration in synovium causing joint destruction and bone erosion. The heterogeneous nature of the disease manifests in different clinical forms, hence treatment of RA still remains obscure. Treatments are limited owing to systemic toxicity by dose-escalation and lack of selectivity. To overcome these limitations, Smart drug delivery systems (SDDS) are under investigation to exploit the arthritic microenvironment either by passive targeting or active targeting to the inflamed joints via folate receptor, CD44, angiogenesis, integrins. This review comprehensively deliberates upon understanding the pathophysiology of RA and role of SDDSs, highlighting the emerging trends for RA nanotherapeutics

Chemical denaturants induced folding unfolding pathway of the recombinant zebrafish dihydrofolate reductase

148-156Denaturation of proteins plays a crucial part in cellular activities. In this study, we have investigated the folding unfolding pathways of zebrafish dihydrofolate reductase (zDHFR) in presence of different chemical denaturants which were found to be an influential factor for the refolding yield by UV-visible spectrophotometric analysis. The activity change of zDHFR has been observed in presence of three different denaturants like Acetic Acid (AcOH), Sodium Dodecyl Sulphate (SDS), and Ethanol (C2H5OH). Spectrophotometric analysis reveals that protein unfolded completely at different concentrations and times by these denaturants. The spontaneous refolding experiments of chemically denatured zDHFR were also conducted to verify the spontaneous refolding yield. These investigations have helped us to decipher a picture about the denaturants contributing to achieving the refolding yield. We observed that acetic acid is a stronger denaturant among all, and the spontaneous refolding yields were higher from SDS denaturation. In the light of the above findings, higher spontaneous refolding yields were obtained from the low concentration of denaturants

Versatility of berberine as an effective immunomodulator and chemo sensitizer against p53 mutant cell

509-520Cancer is the leading cause of death among individuals due to its poor prognosis. Various therapeutics treatments are available in form radiation therapy, chemotherapy, or immunotherapy but major point of concern is the treatment of cancer resistant cell lines. Homozygous loss of the p53 gene is virtually present in every type of cancer. Mutation in DNA binding domain of p53 leads to formation of mutant forms having altered amino acid sequence which lacks DNA binding activity. Berberine is chemo-sensitizing isoquinoline quaternary alkaloid molecule obtained from Berberis vulgaris. Berberine has the capability to suppress the growth of broad range of tumors. It exhibits pharmacological, biochemical and anticancer properties which can potentiate the activities of the existing therapeutics available in a way that it can re-sensitize the cancer resistant clones. Berberine has an immanent potential to bind with DNA and can communicate with several cellular targets, further it also shows hormetic effect which refers to biphasic dose response curve in order to determine dose dependent stimulatory and inhibitory effect. Mode of action involved is yet not well understood but mechanistic pathway involved are autophagy, up-regulation of tumor-suppressor gene (p53) and epigenetic alterations in the viral DNA. In this review, versatility of berberine can be utilized ideally or in combination with chemotherapeutics drugs to potentiate chemo sensitization of the resistant cancer cell line. Further, cancer cell specific receptor targeting can also be employed in combination with berberine for therapeutic treatment of metastasizing cancer cells

Synthesis of Zinc Oxide Nanoparticles, its characterization and anti-microbial activity assessment

Zinc oxide nanoparticles (ZnO NPs) are one of the most abundant metal oxides nanoparticles. It provides excellent thermal, electrical and chemical stabilities with low biotoxicity; its photo-oxidising and photo-catalytic impact on biological and chemical species is of great importance, thereby making it a promising candidate to be used for in-vitro and in-vivo studies in biomedical field. Hereby, ZnO NPs were synthesized using precipitation method with zinc acetate and sodium hydroxide as starting materials. This study has characterized the synthesized ZnO NPs using different techniques such as UV-Visible spectroscopy indicating a peak at 365 nm wave length, size of ZnO NPs was determined to be 286.7 nm by measuring hydrodynamic radii using Dynamic Light Scattering (DLS) phenomena. Further predominant charge existing at surface of the synthesised ZnO NPs was evaluated to be 31.6mV. Anti-microbial activity of ZnO NPs was determined by Kirby-Bauer method for both Gram-positive and Gram-negative bacteria, S. aureus and E. colirespectively. Anti-microbial activity was determined as Zone of Inhibition that measures both bactericidal and bacteriostatic activity of ZnO NPs and was found to be more potent for Gram-positive (S. aureus)bacteria and its activity increased with increasing concentration of nanoparticles. Growth kinetics was studied to determine percentage growth inhibition, for this optical density was recorded as a function of time in bacterial culture broth with and without treatment. Further DNA fragmentation assay was performed to determine genotoxicity caused by nanoparticles and its effect on genomic DNA of bacteria. Highlighting its potential role as a nano-carrier system for leading antibacterial drugs for enhanced effectiveness of the antibacterial therapie

Nano-therapeutic efficacy of green synthesized gold nanoparticles (gAuNPs) and its antibacterial efficacy

455-460We report the efficacy of the gold nanoparticles (AuNPs) synthesized using the leaf extracts of Syzygium cumini (common name Jamun) with auric chloride (AuCl4) which was used as both reducing and capping agent at room temperatures- 25°C. Synthesized AuNPs were characterized using UV-Vis spectroscopy indicating a peak in the range of 520-540 nM. The hydrodynamic radii measured by DLS clearly indicated the size of AuNPs in the range of 14-64 nM. The biological efficacy in terms of antimicrobial activity was assessed by the Kirby Bauer method, applied for both Gram-positive and Gram-negative bacteria such as Staphylococcus aureus and Escherichia coli, respectively. The Zone of inhibition (ZOI) diameter was found to be 4 mM and 3 mM in S. aureus and E. coli, as indicated by the bactericidal activity. Hence, AuNPs synthesized by green synthesis are proposed as economical, environment friendly with immense potential as an antibacterial agent and for drug delivery

Iron Oxide-Based Magneto-Optical Nanocomposites for In Vivo Biomedical Applications

Iron oxide nanoparticles (IONPs) have played a pivotal role in the development of nanomedicine owing to their versatile functions at the nanoscale, which facilitates targeted delivery, high contrast imaging, and on-demand therapy. Some biomedical inadequacies of IONPs on their own, such as the poor resolution of IONP-based Magnetic Resonance Imaging (MRI), can be overcome by co-incorporating optical probes onto them, which can be either molecule- or nanoparticulate-based. Optical probe incorporated IONPs, together with two prominent non-ionizing radiation sources (i.e., magnetic field and light), enable a myriad of biomedical applications from early detection to targeted treatment of various diseases. In this context, many research articles are in the public domain on magneto-optical nanoparticles; discussed in detail are fabrication strategies for their application in the biomedical field; however, lacking is a comprehensive review on real-life applications in vivo, their toxicity, and the prospect of bench-to-bedside clinical studies. Therefore, in this review, we focused on selecting such important nanocomposites where IONPs become the magnetic component, conjugated with various types of optical probes; we clearly classified them into class 1 to class 6 categories and present only in vivo studies. In addition, we briefly discuss the potential toxicity of such nanocomposites and their respective challenges for clinical translations

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Downmodulation of lysophosphatidic acid by Berberine loaded folate-conjugated glycol chitosan nanoparticles (BFGCN) to mitigate Rheumatoid arthritis (RA) & Cardio-vascular disease(CVD): Current knowledge and future perspectives

The perils of cardiovascular diseases (CVD) are enhanced by systemic chronic inflammation in autoimmune disorders like Rheumatoid arthritis (RA), in which the patients generally exhibit a high inflammatory burden, dyslipidemia causing 50-60% of RA patients susceptible to CVD dependent mortality. Lysophosphatidic acid (LPA) is a polar, pleiotropic lipid molecule that is water soluble and present in the synovial fluid that can be exploited as an effective biomarker for lipid-signalling. Current research on alternative medicine has recognized various new molecular targets of Berberine (BBR) and established novel signals in support of the efficacy and therapeutic potential of BBR to fight CVD. Therefore, BBR, an alkaloid with poor aqueous solubility could be foreseen as a therapeutic strategy for the reduction of inflammation induced lipidemia by targeting the macrophages and modulating their functions. Hence, a novel BBR loaded folate-conjugated glycol chitosan nanoparticles (BFGCN) could be hypothesized as a three-pronged approach to target activated macrophages, fibroblasts of synovial fluid for downmodulation of LPA. The greatest challenge is the heterogeneity, complexity and interdependence of RA and CVD. Investigation of prognostic and predictive biomarkers is urgently required. Therefore, an improved understanding of the pathogenesis of RA would facilitate identifying an improved targeted treatment and management of RA patients