Progress and prospects in the management of bacterial infections and developments in Phytotherapeutic modalities

The advent of antibiotics revolutionized medical care resulting in significantly reduced mortality and morbidity caused by infectious diseases. However, excessive use of antibiotics has led to the development of antibiotic resistance and indeed, the incidence of multidrug-resistant pathogens is considered as a major disadvantage in medication strategy, which has led the scholar's attention towards innovative antibiotic sources in recent years. Medicinal plants contain a variety of secondary metabolites with a wide range of therapeutic potential against the resistant microbes. Therefore, the aim of this review is to explore the antibacterial potential of traditional herbal medicine against bacterial infections. More than 200 published research articles reporting the therapeutic potential of medicinal plants against drug-resistant microbial infections were searched using different databases such as Google Scholar, Science Direct, PubMed and the Directory of Open Access Journals (DOAJ), etc., with various keywords like medicinal plants having antibacterial activities, antimicrobial potentials, phytotherapy of bacterial infection, etc. Articles were selected related to the efficacious herbs easily available to local populations addressing common pathogens. Various plants such as Artocarpus communis, Rheum emodi, Gentiana lutea L., Cassia fistula L., Rosemarinus officinalis, Argemone maxicana L, Hydrastis canadensis, Citrus aurantifolia, Cymbopogon citrates, Carica papaya, Euphorbia hirta, etc, were found to have significant antibacterial activities. Although herbal preparations have promising potential in the treatment of multidrug-resistant bacterial infection, still more research is required to isolate phytoconstituents, their mechanism of action as well as to find their impacts on the human body.     

Incidental findings in emergency imaging: frequency,recommendations, and compliance with consensus guidelines

The purpose of this study was to evaluate the frequency of incidental findings (IFs) in emergency department (ED) imaging reports and evaluate the adherence of imaging recommendations to consensus societal guidelines for IFs. A retrospective review of consecutive ED computed tomography (CT) and ultrasonography (US) reports from two university-affiliated EDs over a 2-month period was performed. Each imaging report was reviewed in its entirety, and incidental findings were documented along with recommendations for additional imaging. Imaging recommendations were compared to published societal guidelines from the American College of Radiology (ACR) and Fleischner Society. Three thousand one hundred thirty-one total cases consisting of 1967 CTs and 1164 US contained 514 incidental findings (16.4 %), with 329 CT IFs (64 %) and 185 US IFs (36 %). The ovary was the most common organ for an IF (n?=?214, 42 %). Of all IFs, 347 (67.5 %) recommendations were concordant with societal guidelines and 167 (32.5 %) were discordant. 39.8 % of CT recommendations were discordant, while 19.5 % of US recommendations were discordant (p?<?0.0001). Incidental findings are commonly encountered in the emergent setting. Variable adherence to societal guidelines is noted. Targeted radiologist education and technological solutions may decrease rates of discordance.     

3,4‐Dihydroxybenzaldehyde lowers ROS generation and protects human red blood cells from arsenic(III) induced oxidative damage

Arsenic (As) is a potent environmental toxicant and chronic exposure to it results in various malignancies in humans. Oxidative stress has been implicated in the etiopathogenesis of As‐induced toxicity. This investigated the protective effect of plant antioxidant 3,4‐dihydroxybenzaldehyde (DHB) on sodium meta‐arsenite (SA), an As‐(III) compound, induced oxidative damage in human red blood cells (RBC). The RBC were first incubated with different concentrations of DHB and then treated with SA at 37°C. Hemolysates were prepared and assayed for various biochemical parameters. Treatment of RBC with SA alone enhanced the generation of reactive oxygen species and increased lipid and protein oxidation. Reduced glutathione levels, total sulfhydryl content and cellular antioxidant power were significantly decreased in SA alone treated RBC, compared to the untreated control cells. This was accompanied by membrane damage, alterations in activities of antioxidant enzymes and deranged glucose metabolism. Incubation of RBC with DHB, prior to treatment with SA, significantly and dose‐dependently attenuated the SA‐induced changes in all these parameters. Scanning electron microscopy of RBC confirmed these biochemical results. Treatment of RBC with SA alone converted the biconcave discoids to echinocytes but the presence of DHB inhibited this conversion and the RBC retained their normal shape. These results show that DHB protects human RBC from SA‐induced oxidative damage, most probably due to its antioxidant character.     

Bamboo leaf-based carbon dots for efficient tumor imaging and therapy

In this study, carbon dots synthesized from bamboo leaf cellulose were used simultaneously as a staining agent and for doxorubicin delivery to target cancer cells. Owing to their nontoxic properties, the production of carbon dots from bamboo leaves is a green approach involving optimized application of bamboo tree waste. For multifunctional applications, the carbon dots were modified with 4-carboxybenzylboronic acid and doxorubicin to improve target specificity and drug delivery to HeLa tumor cells. The resulting modified carbon dots were characterized using different analytical techniques, which showed that they were biocompatible, nontoxic, and highly stable over a wide range of pH values and at high ionic strengths. Furthermore, in vitro confocal microscopy studies demonstrated their blue fluorescence and cellular pathway for entering HeLa cells via folate receptor-mediated endocytosis. Cell viability data and flow cytometry results also confirmed the selective uptake of the carbon dots by HeLa cells, which significantly enhanced cell cytotoxicity.

In this study, carbon dots synthesized from bamboo leaf cellulose were used simultaneously as a staining agent and for doxorubicin delivery to target cancer cells.     

Microwave-assisted facile synthesis of poly(luminol-co-phenylenediamine) copolymers and their potential application in biomedical imaging

Conjugated copolymers have attracted much attention because of their outstanding photo-physical properties. The present work reports for the first time, microwave-assisted copolymerization of o-phenylenediamine with luminol using different weight ratios of the two monomers. The composition of the copolymers was confirmed by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (¹H-NMR) while monomer reactivity ratios were determined using the Fineman–Ross method. Ultraviolet-visible spectroscopy revealed the variation in polaronic states upon copolymerization while X-ray diffraction (XRD) and transmission electron microscopy (TEM) analyses showed the morphology of the copolymers to be intermediate between that of the homopolymers. Confocal analysis and fluorescence studies revealed that the copolymers showed composition based blue as well as red emission which could be utilized for in vivo imaging of cancer cells.

Development of bioimaging agents based on poly(o-phenylendiamine and luminol).     

Tunable Pseudo-Piezoelectric Effect in Doped Calcium Titanate for Bone Tissue Engineering

CaTiO₃ is a promising candidate as a pseudo-piezoelectric scaffold material for bone implantation. In this study, pure and magnesium/iron doped CaTiO₃ are synthesized by sol-gel method and spark plasma sintering. Energy dispersive X-ray mapping confirm the homogenous distribution of doping elements in sintered samples. High-energy X-ray diffraction investigations reveal that doping of nanostructured CaTiO₃ increased the strain and defects in the structure of CaTiO₃ compared to the pure one. This led to a stronger pseudo-piezoelectric effect in the doped samples. The charge produced in magnesium doped CaTiO₃ due to the direct piezoelectric effect is (2.9 ± 0.1) pC which was larger than the one produced in pure CaTiO₃ (2.1 ± 0.3) pC, whereas the maximum charge was generated by iron doped CaTiO₃ with (3.6 ± 0.2) pC. Therefore, the pseudo-piezoelectric behavior can be tuned by doping. This tuning of pseudo-piezoelectric response provides the possibility to systematically study the bone response using different piezoelectric strengths and possibly adjust for bone tissue engineering.     

Membranous Nephropathy With Crescents in a Patient With Hashimoto’s Thyroiditis: A Case Report

Membranous nephropathy is a common cause of nephrotic syndrome in adults. It usually occurs secondary to underlying disease processes such as autoimmune disorders, malignancy, infection, and drugs. The presentation of nephrotic syndrome with concomitant precipitous decline in renal function warrants investigation of a coexistent disorder.We report the case of a 30-year-old male who presented with symptoms and signs of hypothyroidism.A diagnosis of Hashimoto’s thyroiditis was contemplated based on the presence of high serum levels of antithyroglobulin and antithyroid peroxidase antibodies. Upon initiation of treatment with levothyroxine, patient symptomatology improved; however, the laboratory studies demonstrated continued elevated creatinine, hematuria, and proteinuria, which had not been addressed. Two months following treatment initiation, he had progressive deterioration in renal function and proteinuria. A renal biopsy revealed coexistent necrotizing and crescentic glomerulonephritis and membranous nephropathy.The final diagnosis was necrotizing, crescentic glomerulonephritis with superimposed membranous nephropathy likely secondary to Hashimoto’s thyrodiitis.Induction treatment with oral cyclophosphamide and prednisone was started.At the end of 6 months of treatment, there was improvement in renal function and proteinuria and maintenance treatment with azathioprine and low-dose prednisone was initiated. This case highlights the importance of precise and detailed evaluation of patients with autoimmune diseases such as Hashimoto’s thyroiditis particularly in the presence of active urine sediment. Proper evaluation and diagnosis of such patients has implications on the prognosis and response to treatment.     

Venetoclax and hypomethylating agents in FLT3-mutated acute myeloid leukemia

FMS-like tyrosine kinase 3 (FLT3) mutations are prevalent in acute myeloid leukemia (AML), and their presence confers adverse risk. FLT3-mutated (FLT3m) AML is a challenging leukemia to manage, particularly in older and unfit patients as well as patients with relapsed/refractory (r/r) disease. We retrospectively analyzed the outcomes of 50 FLT3m AML patients (17 treatment-naïve, 33 r/r) treated with venetoclax (VEN) and hypomethylating agents (HMA). The overall CR/CRi rate with VEN-HMA was 60% (94% in treatment-naïve AML and 42% in r/r AML). Early (60-days) treatment related mortality was 2%. The r/r AML setting was an independent predictor of lower complete response (OR: 0.08; 95%CI: 0.00-0.60, P = .03). Cytogenetics-molecular risk, concurrent mutations, the type of FLT3 mutation (ITD vs TKD), the ITD allelic ratio, the type of HMA, age, prior exposure to HMA and receipt of prior allogeneic transplant did not independently impact response or leukemia-free survival (LFS). Concurrent IDH mutations were associated with lower CR/CRi (P = .01), while ASXL1 or TET2 mutations showed a non-significant association toward higher CR/CRi (P = .07, for both). However, none of the concurrent mutations were an independent predictor for response when adjusted to AML setting. In conclusion, VEN-HMA is associated with encouraging efficacy in FLT3m AML among both newly diagnosed unfit and r/r patients.