Metatranscriptomic profiles reveal the biotransformation potential of azithromycin in river periphyton.

Assessment of the interaction between the biotransformation of chemical contaminants and enzyme activity from aquatic microbial communities is critical for improving the micropollutant degradation in river remediation. Here, association mining based on metatranscriptomic analysis was initially applied to determine the genes encoding enzymes involved in the azithromycin (AZI) transformation process and the corresponding microbial hosts in periphyton, followed by revealing the dynamic variation in the community structure and function. In terms of the biotransformation potential, the highly correlated 15 enzymes were suggested to be primarily involved in AZI biotransformation, energy supply, and antibiotic resistance processes, especially aryl-alcohol dehydrogenases (EC: 1.1.1.90), hydroxylamine dehydrogenase (EC: 1.7.2.6), and monooxygenases (EC: 1.14.11.57) that were involved in the biotransformation of AZI. In the matter of community ecological function, the photosystem II (PSII) reaction center in the periphytic photosynthetic process, as indicated by Fv/Fm, was inhibited after AZI exposure, which may be attributed to the down-regulated genes enriched in the photosynthesis - antenna proteins (ko00196), photosynthesis (ko00195), and two-component system (ko02020) pathways. Furthermore, the periphytic utilization capacity for carbohydrates and phenolic acids was enhanced, which was in accordance with all the increased expression of transcripts involved in the corresponding molecular pathways, including aminobenzoate degradation (ko00627), starch and sucrose metabolism (ko00500), ABC transporters (ko02010), phosphotransferase system (ko02060), galactose metabolism (ko00052), amino sugar and nucleotide sugar metabolism (ko00520). Taken together, this study highlighted the critical role of river periphyton in the micropollutant degradation and unraveled the molecular mechanism of antibiotic biotransformation as well as the structural and functional damage in the periphyton.

Fractional Laser Resurfacing for Acne Scars: Our Experience at Tertiary Care Hospital of North India.

Background: Acne is very common among adolescents, which may sometimes persist into adulthood, and acne scars continue to have a profoundly negative impact on quality of life. Of all the various modalities available, fractional lasers have shown effective results. Aims and Objectives: The aim of this study was to assess the efficacy and safety of fractional carbon dioxide (CO2) laser resurfacing in atrophic facial acne scars. Materials and Methods: The study included 104 subjects aged ≥18 years with atrophic acne scars on face of more than 6 months of duration recruited over a period of 1 year. All the patients were treated with fractional CO2 laser (600 W power and wavelength 10,600 nm). Four sessions of fractional CO2 laser resurfacing were done at 6-week intervals in each patient. We compared the improvement rate of scars after every session at 6-week interval, 2 weeks after the last session, and finally 6 months after the last laser session. Results: The difference between the mean baseline score (3.43) and mean final score (1.83) using Goodman and Baron's qualitative scar scale was found to be statistically significant (P = 0.001). Mean improvement increased from first treatment session to the end of the treatment course from 0.56 to 1.62 indicating the role of the number of sessions in the overall improvement of acne scars. With regard to overall satisfaction, maximum number of patients were either very satisfied (55.8%) or satisfied (25%) as compared to those who were only slightly satisfied (11.5%) or completely unsatisfied (7.7%). Conclusion: Fractional ablative laser gives excellent results in the management of acne scars and has emerged as an appealing non-invasive option for this indication. Being a safe and effective option for atrophic acne scar treatment, it can be recommended wherever available.

Surface engineered mesoporous silica carriers for the controlled delivery of anticancer drug 5-fluorouracil: Computational approach for the drug-carrier interactions using density functional theory.

Introduction: Drug delivery systems are the topmost priority to increase drug safety and efficacy. In this study, hybrid porous silicates SBA-15 and its derivatives SBA@N and SBA@3N were synthesized and loaded with an anticancer drug, 5-fluorouracil. The drug release was studied in a simulated physiological environment. Method: These materials were characterized for their textural and physio-chemical properties by scanning electron microscopy (SEM), nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), small-angle X-ray diffraction (SAX), and nitrogen adsorption/desorption techniques. The surface electrostatics of the materials was measured by zeta potential. Results: The drug loading efficiency of the prepared hybrid materials was about 10%. In vitro drug release profiles were obtained in simulated fluids. Slow drug release kinetics was observed for SBA@3N, which released 7.5% of the entrapped drug in simulated intestinal fluid (SIF, pH 7.2) and 33% in simulated body fluid (SBF, pH 7.2) for 72 h. The material SBA@N presented an initial burst release of 13% in simulated intestinal fluid and 32.6% in simulated gastric fluid (SGF, pH 1.2), while about 70% of the drug was released within the next 72 h. Density functional theory (DFT) calculations have also supported the slow drug release from the SBA@3N material. The release mechanism of the drug from the prepared carriers was studied by first-order, second-order, Korsmeyer-Peppas, Hixson-Crowell, and Higuchi kinetic models. The drug release from these carriers follows Fickian diffusion and zero-order kinetics in SGF and SBF, whereas first-order, non-Fickian diffusion, and case-II transport were observed in SIF. Discussion: Based on these findings, the proposed synthesized hybrid materials may be suggested as a potential drug delivery system for anti-cancer drugs such as 5-fluorouracil.

Effects of erythromycin and roxithromycin on river periphyton: Structure, functions and metabolic pathways.

Macrolides have been frequently detected in the surface waters worldwide, posing a threat to the aquatic microbes. Several studies have evaluated the ecotoxicological effects of macrolides on single algal and bacterial strains. However, without considering the species interaction in the aquatic microbial community, these results cannot be extrapolated to the field. Thus, the present study aimed to evaluate the effects of two macrolides (erythromycin and roxithromycin) on the structure, photosynthetic process, carbon utilization capacity, and the antibiotic metabolic pathways in river periphyton. The colonized periphyton was exposed to the graded concentration (0 µg/L (control), 0.5 µg/L (low), 5 µg/L (medium), 50 µg/L (high)) of ERY and ROX, respectively, for 7 days. Herein, high levels of ERY and ROX altered the community composition by reducing the relative abundance of Chlorophyta in the eukaryotic community. Also, the Shannon and Simpson diversity indexes of prokaryotes were reduced, although similar effects were seldomly detected in the low and medium groups. In contrast to the unchanged carbon utilization capacity, the PSII reaction center involved in the periphytic photosynthesis was significantly inhibited by macrolides at high levels. In addition, both antibiotics had been degraded by periphyton, with the removal rate of 51.63-66.87% and 41.85-48.27% for ERY and ROX, respectively, wherein the side chain and ring cleavage were the main degradation pathways. Overall, this study provides an insight into the structural and functional toxicity and degradation processes of macrolides in river periphyton.

Heparin-Loaded Alginate Hydrogels: Characterization and Molecular Mechanisms of Their Angiogenic and Anti-Microbial Potential.

Background: Chronic wounds continue to be a global concern that demands substantial resources from the healthcare system. The process of cutaneous wound healing is complex, involving inflammation, blood clotting, angiogenesis, migration and remodeling. In the present study, commercially available alginate wound dressings were loaded with heparin. The purpose of the study was to enhance the angiogenic potential of alginate wound dressings and analyze the antibacterial activity, biocompatibility and other relevant properties. We also aimed to conduct some molecular and gene expression studies to elaborate on the mechanisms through which heparin induces angiogenesis. Methods: The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR). Swelling ability was measured by soaking hydrogels in the Phosphate buffer at 37 °C, and cell studies were conducted to evaluate the cytotoxicity and biocompatibility of hydrogels in NIH3T3 (fibroblasts). Real-time PCR was conducted to check the molecular mechanisms of heparin/alginate-induced angiogenesis. The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR). Results: FTIR confirmed the formation of heparin-loaded alginate wound dressing and the compatibility of both heparin and alginate. Among all, 10 µg/mL concentration of heparin showed the best antibacterial activity against E. coli. The swelling was considerably increased up to 1500% within 1 h. Alamar Blue assay revealed no cytotoxic effect on NIH3T3. Heparin showed good anti-microbial properties and inhibited the growth of E. coli in zones with a diameter of 18 mm. The expression analysis suggested that heparin probably exerts its pro-angiogenetic effect through VEGF and cPGE. Conclusions: We report that heparin-loaded alginate dressings are not cytotoxic and offer increased angiogenic and anti-bacterial potential. The angiogenesis is apparently taken through the VEGF pathway.

Rituximab in Pemphigus - An Observational Study from a Tertiary Care Center of North India.

Background: Pemphigus is a group of potentially fatal autoimmune mucocutaneous blistering diseases. Rituximab (RTX) is a chimeric anti-CD20 (anti-cluster of differentiate 20) monoclonal antibody being increasingly used and becoming the first-line therapy in the management of pemphigus. Aims and Objectives: This was an observational study to evaluate the efficacy and safety of rituximab in patients of pemphigus vulgaris (PV) who either did not respond or relapsed after conventional therapeutic regimens and in treatment naive pemphigus patients. Materials and Methods: The study included pemphigus patients coming to our immunobullous clinic who did not respond to conventional therapy or relapsed after receiving conventional therapy as well as fresh cases between January 2019 and October 2021. All enrolled patients received two doses of rituximab (1 gram in each) as intravenous infusions two weeks apart as per the rheumatoid arthritis protocol. The efficacy and safety were evaluated by assessing pemphigus area and activity score (PAAS) before and after the therapy, clinical response, and any adverse events during follow-up. Results: Sixteen (ten males and six females) patients were included in the study. The age of these patients ranged from 27 to 60 years, with a mean of 43.8 ± 9.8 years. There were 15 (93.75%) patients with PV (14 mucocutaneous type and 01 mucosal) and one (6.25%) with pemphigus foliaceus. Among these patients, nine (56.25%) were relapse cases, four (25%) were non-responders, and three (18.75%) were fresh cases who received rituximab as first-line therapy. Fourteen (87.5%) patients reached complete remission off therapy over a median time of 6.36 months (ranging from 18 weeks to 35 weeks). Rituximab was well-tolerated by our patients, and no serious adverse events were observed. The main limitation of our study was the small sample size and the lack of a comparison group. Conclusion: Rituximab is a safe and effective treatment for pemphigus.

Intra-individual Right-Left Comparative Study of Combined Therapy of Intramatricial Triamcinolone and Platelet-Rich Plasma vs. Intramatricial Triamcinolone Only in Lichen Planus-Associated Nail Dystrophy.

BACKGROUND: While intramatricial triamcinolone is the most commonly used treatment option for onychodystrophy due to lichen planus, the role of platelet-rich plasma (PRP) in the treatment of onychodystrophy is not established. So we combined the two treatment modalities to assess the synergistic action on nail dystrophy. AIMS AND OBJECTIVES: The aim of this article is to compare the effect of combination of intramatricial triamcinolone and PRP vs. intramatricial triamcinolone alone in the treatment of onychodystrophy. MATERIALS AND METHODS: This study was done in 26 and 25 pairs of symmetrical dystrophic nails in hands and feet, respectively. The patients received intramatricial injection of triamcinolone and PRP on one side of finger and toe nails and triamcinolone on the contralateral side. RESULTS: Statistically significant improvements in grades of dystrophy according to the Nail Dystrophy Grading System (NDGS) in the finger and toe nails treated with combined therapy were obtained (P < 0.001 and = 0.002, respectively). According to the physician global assessment, response to combination therapy was statistically significant between the two comparison groups of finger and toe nails (P = 0.001 and = 0.004, respectively). Similarly, according to the patient satisfaction score, statistically significant difference was found between the comparison groups of combination therapy and single therapy (P < 0.001). CONCLUSION: Addition of PRP significantly improved the nail quality. Intramatricial PRP is a safe and effective therapeutic modality in refractory nail dystrophies.

Akt Downregulates B-Cell Translocation Gene-2 Expression Via Erk1/2 Inhibition for Proliferation of Cancer Cells.

B-cell translocation gene 2 (Btg2) is a tumor suppressor gene that is implicated in many biological processes. Akt is a serine/threonine kinase which was originally discovered as an oncogene. The prognostic value of Akt activation in some types of cancers and its effect on tumor suppressor genes remains to be fully elucidated. In the current research we have investigated the Akt-mediated downregulation of Btg2 that increased cells proliferation and cells survival. Human leukemia HL-60, THP-1 and colon cancer DLD-1 cells were used in this study. Inhibition of Akt with LY294002 significantly increased Btg2 mRNA expression while activation of Akt with insulin decreased Btg2 expression. Contrary to this, treatment of cells with U0126, a MAPK kinase inhibitor, significantly abrogated Btg2 expression. Moreover, LY294002 treatment increased Erk1/2 activation, decreased cells proliferation and cells viability while activation of Akt by insulin led to an increase in cells survival and cells division. Exogenous expression of Btg2 decreased cells proliferation both in the presence and absence of insulin and arrested cells at G1 phase. Akt negatively regulates Btg2 via Erk1/2 inhibition that lead to an increase in cells survival and cells proliferation. This elucidates a new mechanism for Btg2 regulation and Akt mediated tumorgenicity.

Nonenzymatic amperometric dopamine sensor based on a carbon ceramic electrode of type SiO2/C modified with Co3O4 nanoparticles.

An amperometric nonenzymatic dopamine sensor has been developed. Cobalt oxide (Co3O4) nanoparticles were uniformly dispersed inside mesoporous SiO2/C. A sol-gel process was used for the preparation of this mesoporous composite material (SiO2/C). This mesoporous composite has a pore size of around 13-14 nm, a large surface area (SBET 421 m2·g-1) and large pore volume (0.98 cm3·g-1) as determined by the BET technique. The material compactness was confirmed by SEM images which showing that there is no phase segregation at the magnification applied. The chemical homogeneity of the materials was confirmed by EDX mapping. The SiO2/C/Co3O4 nanomaterial was pressed in desk format to fabricate a working electrode for nonenzymatic amperometric sensing of dopamine at a pH value of 7.0 and at a typical working potential of 0.25 V vs SCE. The detection limit, linear response range and sensitivity are 0.018 µmol L-1, 10-240 µmol L-1, and 80 µA·µmol L-1 cm-2, respectively. The response timé of the electrode is less than 1 s in the presence of 60 µmol L-1 of dopamine. The sensor showed chemically stability, high sensitivity and is not interfered by other electroactive molecules present in blood. The repeatability of this sensor was evaluated as 1.9% (RSD; for n = 10 at a 40 µmol L-1 dopamine level. Graphical abstract Schematic presentation of the preparation of a nanostructured composite of type SiO2/C/Co3O4 for electrooxidative sensing of dopamine.

Serum Vitamin D Levels and Alopecia Areata- A Hospital Based Case-Control Study from North-India.

BACKGROUND: Alopecia areata (AA) is an autoimmune disease which is characterized by hair loss and affects any hair-bearing area. Low levels of Vitamin D have been implicated in a variety of autoimmune diseases. This study was conducted to assess the levels of Vitamin D in patients with AA and its correlation with severity, pattern, and extent of the disease. MATERIALS AND METHODS: This hospital-based study included 135 cases with AA and 135 age- and sex-matched controls. AA cases were grouped according to the severity, pattern, and extent of the disease. The levels of Vitamin D were assessed and compared between cases and controls and among different groups of cases. The data were analyzed, and the correlation was derived. RESULTS: The more number of patients from the case group had deficient and insufficient levels of Vitamin D as compared to controls, the difference being statistically significant (P = 0.01). A highly significant difference was found in mean Vitamin D levels between cases and controls (P = 0.0004). A negative correlation was found between Vitamin D levels and severity of AA as accessed by SALT score. A negative correlation was also found between Vitamin D levels with pattern and extent of the disease. CONCLUSION: Vitamin D deficiency may be one of the factors having a role either in etiopathogenesis or exacerbation of AA. Supplementation of Vitamin D as a treatment modality may improve the clinical outcome of AA.

Preparation of cellulosic Ag-nanocomposites using an ionic liquid.

Cellulose-based nanocomposites have gained much attention due to their remarkable biological properties such as biodegradability, biocompatibility, and low toxicity. In this research work, 1-h-3-methylimidazolium hydrogen sulfate ionic liquid was employed as an efficient solvent for preparation of cellulosic Ag-nanocomposites (CRC/AgNPs composite) from Neem plant. Ionic liquid plays a dual role in obtaining cellulose-rich compound (CRC; removing lignin and hemicellulose components) and plant's extract (phenolic compounds such as flavonoids, tannins, etc.) that reduces the AgNO3 into AgNPs for preparation of CRC/AgNPs composite. The prepared CRC/AgNPs composite was characterized using XRD, FTIR and SEM techniques. The XRD and FTIR spectral analysis showed the characteristic peaks assigned to cellulosic constituent and AgNPs. SEM analysis revealed the particles in the range from 26 to 56 nm. The CRC/AgNPs composite was evaluated for its antibacterial and mechanical properties. The antibacterial activity against S. aureus and E. coli for CRC/AgNPs composite was observed in comparison to CRC. Cell viability and morphology were performed on MC3T3-E1 cells which showed no as such toxicity for the prepared CRC/AgNPs composite. Moreover, the addition of CRC/AgNPs composite as a filler increased the compression strength of polymeric materials.

Fabrication and performance evaluation of blood compatible hemodialysis membrane using carboxylic multiwall carbon nanotubes and low molecular weight polyvinylpyrrolidone based nanocomposites.

This study focused to optimize the performance of polyethersulfone (PES) hemodialysis (HD) membrane using carboxylic functionalized multiwall carbon nanotubes (c-MWCNT) and lower molecular weight grade of polyvinylpyrrolidone (PVP-k30). Initially, MWCNT were chemically functionalized by acid treatment and nanocomposites (NCs) of PVP-k30 and c-MWCNT were formed and subsequently blended with PES polymer. The spectra of FTIR of the HD membranes revealed that NCs has strong hydrogen bonding and their addition to PES polymer improved the capillary system of membranes as confirmed by Field Emission Scanning Electron Microscope (FESEM) and leaching of the additive decreased to 2% and hydrophilicity improved to 22%. The pore size and porosity of NCs were also enhanced and rejection rate was achieved in the establish dialysis range (<60 kDa). The antifouling studies had shown that NCs membrane exhibited 30% less adhesion of protein with 80% flux recovery ratio. The blood compatibility assessment disclosed that NCs based membranes showed prolonged thrombin and prothrombin clotting times, lessened production of fibrinogen cluster, and greatly suppressed adhesion of blood plasma than a pristine PES membrane. The results also unveiled that PVP-k30/NCs improved the surface properties of the membrane and the urea and creatinine removal increased to 72% and 75% than pure PES membranes. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 513-525, 2019.

Amine bridges grafted mesoporous silica, as a prolonged/controlled drug release system for the enhanced therapeutic effect of short life drugs.

Hybrid mesoporous silica SBA-15, with surface incorporated cross-linked long hydrophobic organic bridges was synthesized using stepwise synthesis. The synthesized materials were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, nitrogen adsorption, X-rays diffraction, thermogravimetry and scanning and transmission electron microscopy. The functionalized material showed highly ordered mesoporous network with a surface area of 629.0m2g-1. The incorporation of long hydrophobic amine chains on silica surface resulted in high drug loading capacity (21% Mass/Mass) and prolonged release of ibuprofen up till 75.5h. The preliminary investigations suggests that the synthesized materials could be proposed as controlled release devices to prolong the therapeutic effect of short life drugs such as ibuprofen to increase its efficacy and to reduce frequent dosage.

Preparation and characterization of glycidyl methacrylate organo bridges grafted mesoporous silica SBA-15 as ibuprofen and mesalamine carrier for controlled release.

Mesoporous silica SBA-15 was synthesized and functionalized with bridged polysilsesquioxane monomers obtained by the reaction of 3-aminopropyltriethoxy silane with glycidyl methacrylate in 2:1 ratio. The synthesized mesoporous silica materials were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, nitrogen adsorption, X-ray diffraction, thermogravimetry and scanning electron microscopy. The nuclear magnetic resonance in the solid state is in agreement with the sequence of carbon distributed in the attached organic chains, as expected for organically functionalized mesoporous silica. After functionalization with organic bridges the BET surface area was reduced from 1311.80 to 494.2m(2)g(-1) and pore volume was reduced from 1.98 to 0.89cm(3)g(-1), when compared to original precursor silica. Modification of the silica surface with organic bridges resulted in high loading capacity and controlled release of ibuprofen and mesalamine in biological fluids. The Korsmeyer-Peppas model better fits the release data indicating Fickian diffusion and zero order kinetics for synthesized mesoporous silica. The drug release rate from the modified silica was slow in simulated gastric fluid, (pH1.2) where less than 10% of mesalamine and ibuprofen were released in initial 8h, while comparatively high release rates were observed in simulated intestinal (pH6.8) and simulated body fluids (pH7.2). The preferential release of mesalamine at intestinal pH suggests that the modified silica could be a simple, efficient, inexpensive and convenient carrier for colon targeted drugs, such a mesalamine and also as a controlled drug release system.

The applicability of ordered mesoporous SBA-15 and its hydrophobic glutaraldehyde-bridge derivative to improve ibuprofen-loading in releasing system.

The mesoporous SBA-15 silica with uniform hexagonal pore, narrow pore size distribution and tuneable pore diameter was organofunctionalized with glutaraldehyde-bridged silylating agent. The precursor and its derivative silicas were ibuprofen-loaded for controlled delivery in simulated biological fluids. The synthesized silicas were characterized by elemental analysis, infrared spectroscopy, (13)C and (29)Si solid state NMR spectroscopy, nitrogen adsorption, X-ray diffractometry, thermogravimetry and scanning electron microscopy. Surface functionalization with amine containing bridged hydrophobic structure resulted in significantly decreased surface area from 802.4 to 63.0 m(2) g(-1) and pore diameter 8.0-6.0 nm, which ultimately increased the drug-loading capacity from 18.0% up to 28.3% and a very slow release rate of ibuprofen over the period of 72.5h. The in vitro drug release demonstrated that SBA-15 presented the fastest release from 25% to 27% and SBA-15GA gave near 10% of drug release in all fluids during 72.5 h. The Korsmeyer-Peppas model better fits the release data with the Fickian diffusion mechanism and zero order kinetics for synthesized mesoporous silicas. Both pore sizes and hydrophobicity influenced the rate of the release process, indicating that the chemically modified silica can be suggested to design formulation of slow and constant release over a defined period, to avoid repeated administration.

Free amino and imino-bridged centres attached to organic chains bonded to structurally ordered silica for dye removal from aqueous solution.

Ordered mesoporous SBA-15 type silica was synthesized by sol gel polymerization and reacted with 3-aminopropyltriethoxysilane (AP) or triethylenetetramine (TE), to attach pendant chains or bridging molecules, with basic centres. The materials were characterized by elemental analysis, infrared spectroscopy, and nuclear magnetic resonance in the solid state, X-ray diffractometry, scanning and transmission electron microscopy. The nitrogen sorption/desorption data for SBA-15 and the organofunctionalized SBA-15AP and SBA-15TE silicas resulted in IV type isotherms with hysteresis loops of the H1 type, surface areas of 800; 213 and 457 m(2) g(-1) and average pore diameters of 8.0; 3.2 and 6.8 nm, respectively. The ordered structural features of the mesoporous silica remained preserved after post-functionalization with pendant and bridged organic chains. Sorption data for organofunctionalized silicas gave highly selective sorption capacities for anionic water soluble Reactive Blue dye, with 0.064 and 0.072 mmol g(-1). Negligible sorption was observed with the unmodified mesoporous silica. The results suggest that organofunctionalized silica can be a simple, efficient, inexpensive and suitable method for the effective and selective removal of anionic organic dye pollutants from aqueous solutions.