Structural basis for the mutation-induced dysfunction of the human IL-15/IL-15α receptor complex.

In silico strategies offer a reliable, fast, and inexpensive, way compared to the clumsy in vitro approaches to boost understanding of the effect of amino acid substitution on the structure and consequently the associated function of proteins. In the present work, we report an atomistic-based, reliable in silico structural and energetic framework of the interactions between the receptor-binding domain of the Interleukin-15 (IL-15) protein and its receptor Interleukin-15α (IL-15α), consequently, providing qualitative and quantitative details of the key molecular determinants in ligand/receptor recognition. Molecular dynamics simulations were used to investigate the dynamic behavior of the specific binding between IL-15 and IL-15α followed by estimation of the free energies via molecular mechanics/generalized Born surface area (MM/GBSA). In particular, residues Y26, E46, E53, and E89 of the IL-15 protein receptor-binding domain are identified as main hot spots, shaping and governing the stability of the assembly. These results can be used for the development of neutralizing antibodies and the effective structure-based design of protein-protein interaction inhibitors against the so-called orphan disease, vitiligo.

Green Synthesis of CeO2 Nanoparticles from the Abelmoschus esculentus Extract: Evaluation of Antioxidant, Anticancer, Antibacterial, and Wound-Healing Activities.

Metal oxide nanoparticles synthesized by the biological method represent the most recent research in nanotechnology. This study reports the rapid and ecofriendly approach for the synthesis of CeO2 nanoparticles mediated using the Abelmoschus esculentus extract. The medicinal plant extract acts as both a reducing and stabilizing agent. The characterization of CeO2 NPs was performed by scanning electron microscopy (SEM), X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-Vis), and Fourier transform infrared spectroscopy (FTIR). The in vitro cytotoxicity of green synthesized CeO2 was assessed against cervical cancerous cells (HeLa). The exposure of CeO2 to HeLa cells at 10-125 µg/mL caused a loss in cellular viability against cervical cancerous cells in a dose-dependent manner. The antibacterial activity of the CeO2 was assessed against S. aureus and K. pneumonia. A significant improvement in wound-healing progression was observed when cerium oxide nanoparticles were incorporated into the chitosan hydrogel membrane as a wound dressing.

Hematological complications under hyper conditions of glucose and distilled water.

This work presents a pilot method of hematological diagnosis about changes in: shape, size and rouleaux formation, cell count of leucocytes and platelet cells in the presence of different glucose [C6H12O6] and water [H2O] concentrations. The 2D microscopic images after addition of ten different glucose concentrations to normal blood (0 mM- 450 mM) revealed the lyses (disintegration) of white blood cells (WBCs). This work provides a baseline to diagnose blood disorders and complications at labs and clinical environment.

Synthesis of CuSe/PVP/GO and CuSe/MWCNTs for their applications as nonenzymatic electrochemical glucose biosensors.

Copper selenide (CuSe) is an inorganic binary compound which exhibits metallic behavior with zero band gap. CuSe has multiple applications in electrocatalysis, photothermal therapy, flexible electronic and solar cells. In the current study, copper selenide based nanocomposites CuSe/PVP/GO and CuSe/MWCNTs were synthesized by using the sol-gel method for application as a non-enzymatic glucose biosensor. Different characterization methods were employed, such as X-ray diffraction (XRD), photoluminescence (PL), Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible (UV-Vis) spectroscopy, and photoluminescence for determining various aspects of CuSe/PVP/GO and CuSe/MWCNTs nanocomposites including phase formation, functional group analysis, band gaps and morphology. Electrochemical impedance spectroscopy (EIS) showed that the resistances of modified electrode/bare electrode were 12.3 kΩ/17.3 kΩ and 6.3 kΩ/17.3 kΩ for CuSe/PVP/GO and CuSe/MWCNTs nanocomposites, respectively. Cyclic voltammetry showed that both CuSe/PVP/GO and CuSe/MWCNTs nanocomposites are promising biosensors for detection and monitoring of the glucose level in an analyte. The sensitivity and limit of detection are 2328 µA mM-1 cm-2/0.2 µM and 4157 µA mM-1 cm-2/0.3 µM for CuSe/PVP/GO and CuSe/MWCNTs, respectively. Chronoamperometry confirmed that our nanocomposite was the best sensor for glucose even in the presence of other interferents like ascorbic acid (AA), uric acid (UA) and dopamine (DA).

Correction: Synthesis of CuSe/PVP/GO and CuSe/MWCNTs for their applications as nonenzymatic electrochemical glucose biosensors.

[This corrects the article DOI: 10.1039/D3RA06713K.].

Development of novel polymer haemoglobin based particles as an antioxidant, antibacterial and an oxygen carrier agents.

This innovative work aims to develop highly biocompatible and degradable nanoparticles by encapsulating haemoglobin (Hb) within poly-ε-caprolactone for novel biomedical applications. We used a modified double emulsion solvent evaporation method to fabricate the particles. A Scanning electron microscope (SEM) characterized them for surface morphology. Fourier Transform Infrared Spectroscopy (FTIR) and Ultraviolet-visible spectroscopies (UV-visible) elucidated preserved chemical and biological structure of encapsulated haemoglobin. The airproof equilibrium apparatus obtained the oxygen-carrying capacity and P50 values. The DPPH assay assessed free radical scavenging potential. The antibacterial properties were observed using four different bacterial strains by disk diffusion method. The MTT assay investigates the cytotoxic effects on mouse fibroblast cultured cell lines (L-929). The MTT assay showed that nanoparticles have no toxicity over large concentrations. The well-preserved structure of Hb within particles, no toxicity, high oxygen affinity, P50 value, and IC50 values open the area of new research, which may be used as artificial oxygen carriers, antioxidant, and antibacterial agents, potential therapeutic agents as well as drug carrier particles to treat the cancerous cells. The novelty of this work is the antioxidant and antibacterial properties of developed nanoparticles are not been reported yet. Results showed that the prepared particles have strong antioxidant and antibacterial potential.

Evaluation and Association of Hematological and Biochemical Parameters of Untreated COVID-19 Patients on the Basis of Differences in Ethnicity and Curcumin as a Possible Treatment.

BACKGROUND: CBC (complete blood count) tests, along with RPM (Renal parameters) and LFT (Liver function tests), are clinically important for coronavirus patients; curcumin can serve as a possible treatment for SARS- CoV. OBJECTIVE: The objective of the study was to determine the relationship of CBC parameters with renal parameters and liver function tests and to develop the hypothesis that curcumin may be the best and non-invasive drug for coronavirus. Materials &Methods: The differences between the results of 91 confirmed cases of covid-19 (symptomatic and asymptomatic) and 100 controls were assessed by an independent t-test and Mann-Witney U Wilcoxon test. Microscopy, hematological tools, and techniques were used to assess the improvements/abnormalities in blood components and parameters. RESULTS: This is a case control study along with the feasibility of curcumin as covid treatment. The association between parameters was assessed by Pearson & Spearman correlation analysis. The level of significance was p<0.05. Changes were observed in urea (p=0.000), creatinine (p=0.02), total bilirubin (P=0.000), SGPT (ALT) (p=0.000), RBC (p=0.001), HGB (p=0.001), MCV (p=0.002), MCH (p=0.03), MPV, PDW, NE%, LY%, and MO% EO% (p=0.00), in comparison to normal controls. Differences in the correlation of electrolytes, RPM, and LFT tests along with CBC parameters in Pakistani and Chinese individuals provided a new idea for using various diagnostic and therapeutic tools in different ethnic groups. The covid-19 infected blood components and parameters showed rapid improvement/recovery, especially the total count of platelets and WBCs (lymphocytes and basophils), HGB, HCT, MCV, and MCH. CONCLUSION: Curcumin drugs can be used as an immediate remedy/treatment to cure COVID-19 patients.

Facile synthesis of a CuSe/PVP nanocomposite for ultrasensitive non-enzymatic glucose biosensing.

Non-enzymatic glucose biosensors show high sensitivity, lower response time, wide linear range and low cost. Copper based composites show excellent electrocatalytic tunability and lead to a better charge transfer in electrochemical non-enzymatic glucose biosensors. In this work, a nanocomposite of polyvinylpyrrolidone (PVP) and copper selenide was synthesized by a facile one pot sol gel method. Synthesized nanomaterials were characterized by XRD, FTIR, UV-visible spectroscopy, SEM, EDS and XPS techniques. Electrochemical behavior was analyzed by cyclic voltammetry (CV), electrochemical impendence (EIS) and chronoamperometry techniques. XRD analysis revealed a hexagonal structure and crystalline nature of CuSe/PVP. FTIR spectra depicted C-N bonding at 1284 cm-1 and C[double bond, length as m-dash]O stretching at 1634 cm-1, which indicated the presence of PVP in the nanocomposite. Stretching at 823 cm-1 was attributed to the presence of copper selenide. UV-visible absorption indicated the bandgap of copper selenide/PVP at 2.7 eV. SEM analysis revealed a flake like morphology of CuSe/PVP. EDS and XPS analysis confirmed the presence of copper and selenium in the prepared nanocomposite. Prior to employing for biosensing applications, it is important to evaluate the antibacterial activity of nanomaterials for long term use in biological in vitro testing. These materials have shown an efficient inhibition zone of 26 mm against Gram negative Pseudomonas at 50 µg ml-1 and MIC value of 10 µg ml-1. Cyclic voltammetry shows that CuSe/PVP is a promising biosensor for monitoring glucose levels in a wide linear range of 0.5 mM to 3 mM at an excellent sensitivity of 13 450 µA mM-1 cm-2 with an LOD of 0.223 µM. Chronoamperometry measurements revealed a selective behavior of CuSe/PVP for glucose biosensing amongst ascorbic acid and dopamine as common interfering molecules. The nanocomposite was stable after 8 repeated cycles with 92% retention for glucose sensing capacity. This is attributed to the stable nature of the CuSe/PVP nanocomposite as well as higher surface area of available active sites. Herein the CuSe/PVP nanocomposite offered reasonable selectivity, high sensitivity wide linear range with very low LOD, as well as being abundant in nature, this Cu based biosensor has promising applications for future point of care tests (POCT).

One-pot hydrothermal synthesis of a carbon quantum dot/CaFe2O4 hybrid nanocomposite for carcinogenic Congo red dye degradation.

Semiconductor materials show a restricted degradation response to organic pollutants due to limited photocatalytic activity under visible light. Therefore, researchers have devoted much attention to novel and effective nanocomposite materials. For the first time, herein, a novel nano-sized semiconductor calcium ferrite modified by carbon quantum dots (CaFe2O4/CQDs) photocatalyst is fabricated via simple hydrothermal treatment for the degradation of aromatic dye using a visible light source. The crystalline nature, structure, morphology, and optical parameters of each of the synthesized materials were investigated using X-ray diffraction spectroscopy (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and UV-visible spectroscopy. The nanocomposite exhibits excellent photocatalytic performance (90% degradation) against Congo red (CR) dye. In addition, a mechanism for CaFe2O4/CQDs improving photocatalytic performance has been proposed. The CQDs in the CaFe2O4/CQD nanocomposite are considered to act as an electron pool and transporter, as well as a strong energy transfer material, during photocatalysis. CaFe2O4/CQDs appear to be a promising and cost-effective nanocomposite for dye-contaminated water purification, according to the findings of this study.

Antibacterial and in vivo toxicological studies of Bi2O3/CuO/GO nanocomposite synthesized via cost effective methods.

In this research work, Bi2O3, Bi2O3/GO and Bi2O3/CuO/GO nanocomposites have been synthesized via an eco-friendly green synthesis technique, solgel route and co-precipitation method respectively for the assessment of antibacterial activity as well as in vivo toxicity. The XRD patterns confirm the formation of Bi2O3, Bi2O3/GO and Bi2O3/CuO/GO nanocomposites showing monoclinic structures. Crystallite size and lattice strain are calculated by Scherrer equation, Scherrer plot and Willimson Hall plot methods. Average crystallite size measured for Bi2O3, Bi2O3/GO and Bi2O3/CuO/GO nanocomposites by Scherrer equation, Scherrer plot and WH-plot methods are (5.1, 13.9, 11.5)nm, (5.4, 14.2, 11.3)nm and (5.2, 13.5, 12.0)nm respectively. Optical properties such as absorption peaks and band-gap energies are studied by UV-vis spectroscopy. The FTIR peaks at 513 cm-1, 553 cm-1 and 855 cm-1 confirms the successful synthesis of Bi2O3, Bi2O3/GO and Bi2O3/CuO/GO nanocomposites. The antibacterial activity of synthesized Bi2O3, Bi2O3/GO and Bi2O3/CuO/GO nanocomposites is examined against two gram-negative (Escherichia coli and pseudomonas) as well as gram-positive bacteria (Bacillus cereus and Staphylococcus aureus) at dose 25 mg/kg and 40 mg/kg by disk diffusion technique. Zone of inhibition for Bi2O3, Bi2O3/GO and Bi2O3/CuO/GO at dose 40 mg/kg against E. coli (gram - ve) are 12 mm, 17 mm and 18 mm respectively and against Pseudomonas (gram - ve) are 28 mm, 19 mm and 21 mm respectively. While the zone of inhibition for Bi2O3/GO and Bi2O3/CuO/GO at dose 40 mg/kg against B. cereus (gram + ve) are 8 mm and 8.5 mm respectively and against S. aureus (gram + ve) are 5 mm and 10.5 mm respectively. These amazing results reveal that Bi2O3, Bi2O3/GO and Bi2O3/CuO/GO nanocomposite as a kind of antibacterial content, have enormous potential for biomedical applications. In addition, the in vivo toxicity of synthesized Bi2O3/CuO/GO nanocomposite is investigated on Swiss Albino mice at dose of 20 mg/kg by evaluating immune response, hematology and biochemistry at the time period of 2, 7, 14 and 30 days. No severe damage is observed in mice during whole treatment. The p value calculated by statistical analysis of hematological and biochemistry tests is nonsignificant which ensures that synthesized nanocomposites are safe and non-toxic as they do not affect mice significantly. This study proves that Bi2O3/CuO/GO nanocomposites are biocompatible and can be explored further for different biomedical applications.

Anterior tension - free repair versus posterior preperitoneal repair for recurrent hernia.

OBJECTIVE: To compare anterior tension-free approach with posterior preperitoneal repair for complications and early recurrence. DESIGN: A randomized clinical trial. PLACE AND DURATION OF STUDY: Combined Military Hospital, Muzaffarabad and Rawalpindi, from March 1997 to December 2002. PATIENTS AND METHODS: Sixty-seven patients with unilateral recurrent inguinal scrotal and irreducible hernias, were randomized to either anterior tension-free or posterior preperitoneal repair. Patients with primary inguinal hernia, patients with class11/111 obesity (BMI > 35) and ASA grade 3 and beyond were excluded. For posterior repair, preperitoneal space was entered through a transverse lower abdominal incision placed 3 cms above inguinal ligament. Anterior repair was done by standard Lichtenstein technique. Forty-two patients were operated under spinal anesthesia while 25 patients had general anesthesia. Follow-up was on 7th and 12th postoperative day, at third month, and then yearly for two years. Main outcome measures were postoperative pain and recovery; postoperative complications related to wound, testicles, sensory nerves; and recurrence. RESULTS: Thirty-four patients had anterior tension-free hernioplasty while 33 patients had posterior preperitoneal repair. Mean operating time was longer for anterior preperitoneal repair as compared to posterior repair (70.1min vs. 62.6 min, p = 0.1). Pain score and hospital stay was same for both groups. Return to normal activity was not significantly different being 14.1 days for anterior and 13 days for posterior repair (p= 0.07). Heavy duties were also resumed after statistically non-significant interval, 34.6 days for anterior, and 33 days for posterior repair (p = 0.09). Complication rate in anterior hernioplasty group was 17.6% while in preperitoneal group it was 3% ( p=0.001). There was no recurrence in either group after a mean follow-up of 2 years. CONCLUSION: Open preperitoneal repair and anterior tension-free repair were equivalent in terms of postoperative pain, recovery and early recurrence rate. Considering fewer testicular complications with posterior repair, it should be the procedure of choice for repair of recurrent groin hernia in men.

Prolene Darn: safe and effective method for primary inguinal hernia repair.

OBJECTIVE: The purpose of the study was to evaluate darn repair in terms of morbidity and recurrence rate. DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Combined Military Hospital, Muzaffarabad from February 1997 to April 2001. SUBJECT AND METHODS: Four hundred and sixty-five consecutive patients above the age of 20 years, with primary inguinal hernia underwent darn repair using polypropylene suture. Two hundred and forty-two patients were operated under spinal anaesthesia, 100 under local anaesthesia while 123 patients had general anaesthesia. Patients were examined on 7th and 12th postoperative day for early complications. Subsequently, they were examined at third month, six-month and then yearly for three years. RESULTS: Mean age in our study was 52 years (range 20-75). Indirect hernia was present in 305 (65.5%) patients while 160(34.5%) patients had direct hernia. There were 11 (2.4%) postoperative wound infections. Three (0.6%) patients had hematoma formation. Twenty-one (4.5%) patients went into postoperative urinary retention. Three (0.6%) patients developed recurrence; all these patients were among those who had postoperative wound infection. There was no seroma formation. None of the patients developed any testicular complication or postoperative hydrocele. There was no case of dysejaculation or chronic residual neuralgia. CONCLUSION: It can be concluded from our results that darn repair using non-absorbable suture is safe procedure. It is easily performed and has a very low recurrence rate which is comparable to any other procedure for primary inguinal hernia.