Optimization, In Vitro and Ex Vivo Assessment of Nanotransferosome Gels Infused with a Methanolic Extract of Solanum xanthocarpum for the Topical Treatment of Psoriasis.

The goal of this investigation is to improve the topical delivery of medicine by preparing and maximizing the potential of a nanotransferosome gel infused with Solanum xanthocarpum methanolic extract (SXE) to provide localized and regulated distribution. Thin-film hydration was used to create SXE-infused nanotransferosomes (SXE-NTFs), and a Box-Behnken design was used to improve them. Phospholipon 90G (X1), cholesterol (X2) and sodium cholate (X3) were chosen as the independent variables, and their effects on vesicle size (Y1), polydispersity index (PDI) (Y2) and the percentage of entrapment efficiency (EE) (Y3) were observed both individually and in combination. For the SXE-NTFs, the vesicle size was 146.3 nm, the PDI was 0.2594, the EE was 82.24 ± 2.64%, the drug-loading capacity was 8.367 ± 0.07% and the drug release rate was 78.86 ± 5.24%. Comparing the antioxidant activity to conventional ascorbic acid, it was determined to be 83.51 ± 3.27%. Ex vivo permeation tests revealed that the SXE-NTF gel (82.86 ± 2.38%) considerably outperformed the SXE gel (35.28 ± 1.62%) in terms of permeation. In addition, it seemed from the confocal laser scanning microscopy (CLSM) picture of the Wistar rat's skin that the rhodamine-B-loaded SXE-NTF gel had a higher penetration capability than the control. Dermatokinetic studies showed that the SXE-NTF gel had a better retention capability than the SXE gel. According to the experimental results, the SXE-NTF gel is a promising and successful topical delivery formulation.

Molecular Modeling Study of Novel Lancifolamide Bioactive Molecule as an Inhibitor of Acetylcholinesterase (AChE), Herpes Simplex Virus (HSV-1), and Anti-proliferative Proteins.

Combretaceae, an immense family involving species (500) or genera (20), originates in tropical and subtropical regions. This family has evinced medicinal values such as anti-leishmanial, cytotoxic, antibacterial, antidiabetic, antiprotozoal, and antifungal properties. Conocarpus lancifolius (C. lancifolius) methanol extract (CLM) was prepared, then compound isolation performed by open column chromatography, and compound structure was determined by spectroscopic techniques (13C NMR, IR spectroscopy, 1H-NMR, mass spectrometry UV-visible, and 2D correlation techniques). Molecular docking studies of ligand were performed on transcriptional regulators 4EY7 and 2GV9 to observe possible interactions. Phytochemical screening revealed the presence of secondary metabolites including steroids, cardiac glycosides, saponins, anthraquinones, and flavonoids. The isolated compound was distinguished as lancifolamide (LFD). It showed cytotoxic activity against human breast cancer, murine lymphocytic leukemia, and normal cells, human embryonic kidney cells, and rat glioma cells with IC50 values of 0.72 µg/mL, 2.01 µg/mL, 1.55 µg/mL, and 2.40 µg/mL, respectively. Although no cytotoxic activity was noticed against human colon cancer and human lung cancer, LFD showed 24.04% inhibition against BChE and 60.30% inhibition against AChE and is therefore beneficial for Alzheimer's disease (AD). AChE and LFD interact mechanistically in a way that is optimum for neurodegenerative disorders, according to molecular docking studies. Methanol and dichloromethane extract of C. lancifolius and LFD shows antibacterial and antifungal activity against antibiotic resistance Bacillus subtilis, Streptococcus mutans, Brevibacillus laterosporus, Salmonella Typhi, Candida albicans, and Cryptococcus neoformans, respectively. LFD shows antiviral activity against HSV-1 with 26% inhibition IP. The outcomes of this study support the use of LFD for cognitive disorders and highlight its underlying mechanism, targeting AChE, DNA-POL, NF-KB, and TNF-α, etc., for the first time.

Exploring Liposomes for Lung Cancer Therapy.

Cancer is referred to as a pleiotropic disease-causing approximately 9.6 million deaths in 2018. Among all cancers, lung cancer was the leading cause of death in 2017, and 12% of fatalities were alone due to lung cancer. The associated risk factors in lung cancer include smoking (80-85%), chronic inflammation in the lungs, COPD, pulmonary fibrosis, environmental and occupational exposure to nickel, arsenic, chromates, etc. Early diagnosed patients' treatment plan includes chemotherapy, immunotherapy, radiotherapy, surgery, and tumor ablation. Many sorts of drug delivery carriers have been used in the past, usually in targeted chemotherapy. Liposomes are spherical shape vesicles containing a lipid bilayer and aqueous core, with potency to encapsulate both hydrophobic and hydrophilic drugs with minimal toxicity. These vesicles have a particle size of 0.02-1000 µm allowing selective passive targeting to the tumor's deeper tissues. Current publications on liposomes highlight their acceptance and best choice among all systems to deliver synthetic and herbal drugs to the lungs. This review focuses on many aspects, which include an in-depth analysis of potential anticancer drugs that have utilized the advantages of liposomes for effective lung carcinomatherapy and devices used to deliver the active agents to the pulmonary tissues. Investigations on ongoing, approved, and failed clinical trials and patents on products related to lung cancer have been highlighted to provide a critical review on the subject.

Hyperbaric oxygen therapy for the treatment of long COVID: early evaluation of a highly promising intervention.

BACKGROUND: Long COVID is a common occurrence following COVID-19 infection. The most common symptom reported is fatigue. Limited interventional treatment options exist. We report the first evaluation of hyperbaric oxygen therapy (HBOT) for long COVID treatment. METHODS: A total of 10 consecutive patients received 10 sessions of HBOT to 2.4 atmospheres over 12 days. Each treatment session lasted 105 minutes, consisting of three 30-minute exposures to 100% oxygen, interspersed with 5-minute air breaks. Validated fatigue and cognitive scoring assessments were performed at day 1 and 10. Statistical analysis was with Wilcoxon signed-rank testing reported alongside effect sizes. RESULTS: HBOT yielded a statistically significant improvement in the Chalder fatigue scale (p=0.0059; d=1.75 (very large)), global cognition (p=0.0137; d=-1.07 (large)), executive function (p=0.0039; d=-1.06 (large)), attention (p=0.0020; d=-1.2 (very large)), information processing (p=0.0059; d=-1.25 (very large)) and verbal function (p=0.0098; d=-0.92 (large)). CONCLUSION: Long COVID-related fatigue can be debilitating, and may affect young people who were previously in economic employment. The results presented here suggest potential benefits of HBOT, with statistically significant results following 10 sessions.

Phytochemical composition and In-vitro activity of ethanolic extract of Eucalyptus globulus leaves against multidrug resistant poultry pathogens.

Aim of the present study was to determine the In-vitro antibacterial activity of ethanolic extract of E. globulus leaves against common multidrug resistant poultry pathogens. Phytochemical analysis through HPLC revealed that kaempeferol (7.315min) followed by querecetin (6.655min) and myrecetin (3.655min). Percent area of kaempeferol (6826.88%) was highest, followed by myrecetin (5516.22%) and querecetin (163.748%). Phytochemical investigation of ethanolic extract of E. globulus leaves through GCMS showed highest retention time (min) α-pinene (20.43) and α-terpineol (20.15) accompanied by spathulenol (11.97), piperitone (11.04). The ethanolic extracts of E. globulus leaves showed a highest zone of inhibition against S. pullorum SP6; 20.64± 2.08, E. coli SE 12; 19.75± 2.83, C. perfringens type A (CPM38-01); 19.46± 2.02. The highest level of MIC of E. globulus noted were against S. gallinarum S22; 133.37±53.294, S. gallinarum S1; 130.20±45.10, S. gallinarum S4; 129.47±24.182, S. gallinarum S3; 126.83±72.392. In conclusion, the study confirmed that the ethanolic extract of E. globulus is composed of active ingredients having antibacterial activity and can be referred as an alternate to antibiotics.

Activity of ethanolic extract of Eucalyptus globulus leaves against multi drug resistant poultry pathogens in broiler chicks.

The present study was designed to evaluate the antimicrobial activity of E. globulus leaves in broiler chicks. Total (n=255) day-old chicks were segregated into five groups i.e. Pathogenic E. coli, S. pullorum, S. gallinarum and C. perfringens type A and control negative group. Each bacterial challenged (1x 107 CFU) group was divided into control positive, antibiotic, probiotic and E. globulus group. Experimental birds were exposed to E. coli, S. pullorum, S. gallinarum and C. perfringens type A at different ages. At 35th day of experiment the log reduction for each group was determined. The highest log reduction in E. coli and C. perfringens Type A colonies count were found in E. globulus (3.26) (2.33) treated group followed by antibiotic (2.85) (1.59) and probiotic (2.84) (1.50) respectively. The log reduction in S. pullorum colonies count was highest in E. globulus (2.50) followed by probiotic (2.24) and antibiotic (2.16). The S. gallinarum colonies count log reduction was found highest for antibiotic (2.84) followed by probiotic (2.48) and E. globulus group. The results of in-vivo experiment revealed that ethanolic extract of E. globulus has antibacterial activity and it can be used as a replacement to low level of antibiotics added in poultry feed.

A Systematic Review to Assess the Impact of Hyperbaric Oxygen Therapy on Glycaemia in People with Diabetes Mellitus.

Background and Objectives: Hyperbaric oxygen is a recognised treatment for a range of medical conditions, including treatment of diabetic foot disease. A number of studies have reported an impact of hyperbaric oxygen treatment on glycaemic control in patients undergoing treatment for diabetic foot disease. There has been no systematic review considering the impact of hyperbaric oxygen on glycaemia in people with diabetes. Materials and Methods: A prospectively PROSPERO-registered (PROSPERO registration: CRD42021255528) systematic review of eligible studies published in English in the PUBMED, MEDLINE, and EMBASE databases, based on the following search terms: hyperbaric oxygen therapy, HBO2, hyperbaric oxygenation, glycaemic control, diabetes, diabetes Mellitus, diabetic, HbA1c. Data extraction to pre-determined piloted data collection form, with individual assessment of bias. Results: In total, 10 eligible publications were identified after screening. Of these, six articles reported a statistically significant reduction in blood glucose from hyperbaric oxygen treatment, while two articles reported a statistically significant increase in peripheral insulin sensitivity. Two articles also identified a statistically significant reduction in HbA1c following hyperbaric oxygen treatment. Conclusions: There is emerging evidence suggesting a reduction in glycaemia following hyperbaric oxygen treatment in patients with diabetes mellitus, but the existing studies are in relatively small cohorts and potentially underpowered. Additional large prospective clinical trials are required to understand the precise impact of hyperbaric oxygen treatment on glycaemia for people with diabetes mellitus.

Cardioprotective, hypotensive and toxicological studies of Populus ciliata (Wall. ex Royle).

Populus ciliata Wall ex. Royle has folkloric repute to treat various cardiovascular ailments and related disorders. The current study was designed to evaluate the toxic profile, cardioprotective and hypotensive effects of Populus ciliata (Wall. ex Royle). Populus ciliata crude ethanolic extract (Pc. Cr) and its aqueous (Pc. Aq) & organic (Pc. Dcm) fractions were tested on isolated aorta of rat and rabbit having intact and non-intact endothelium respectively. Pc. Cr & Pc. Aq relaxed the contractions induced by PE (1 µM)-induced and K+ (80 mM)-induced on aorta, possibly by mediating endothelium derived relaxing factor (EDRF) in intact endothelium and voltage dependent L-type calcium channels blocking (CCB) mechanism in non-intact endothelium. Pc. Cr showed anti-hypertensive & cardioprotective activity by decreasing force of contraction & heart rate on isolated rabbit paired atria and reduced blood pressure in anesthetized rat. Cardioprotective effect of Pc. Cr was assessed in isoproterenol induced acute myocardial infarction (AMI) and left ventricular hypertrophy (LVH) in Sprague Dawley rats. In LVH, Pc. Cr exerted positive effects by decreasing angiotensin II & renin and increasing cGMP & nitric oxide (NO) with reduced cardiac fibrosis, necrosis and cardiac cell size. In AMI, Pc. Cr responded effectively by decreasing cardiac markers creatinine kinase (CK), creatinine kinase myocardial band (CK-MB) and lactate dehydrogenase (LD) in blood associated with less edema and necrosis. Presence of catechin, vinallic acid, P-coumeric acid and quercitin identified through HPLC support the effectiveness of Pc. Cr in hypertension, AMI and LVH. Pc. Cr showed no significant adverse effects in Sprague Dawley albino rats after acute & sub-acute treatment in histopathological investigation. Extract of Populus ciliata showed vasorelaxant, hypotensive and cardioprotective effect in Sprague Dawley albino rats and white albino rabbit by mediating EDRF and voltage dependent L-type CCB mechanism respectively.

Effects of diallyl trisulfide, an active substance from garlic essential oil, on structural chemistry of chitin in Sitotroga cerealella (Lepidoptera: Gelechiidae).

The environmental pollution, evolution of resistance, and risks to human and aquatic animal health associated with pesticide application have attracted much attention globally. Herein, we tested the capacity of diallyl trisulfide (DAT) from garlic essential oil to control the destructive stored-product pest, Sitotroga cerealella. The effects of DAT on the total content of cuticular chitin and structure of adults S. cerealella were evaluated. This study was the first to investigate changes in chitin structure in adults due to exposure to DAT through Fourier-transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, and differential scanning calorimetry. The results of these analyses revealed that the cuticular chitin content of pests decreased after DAT treatment. DAT treatment also reduced thermal stability and crystallinity of chitin. These findings indicate that DAT is a potent biopesticide that is active against the moth, and establishes the basis for its use as an IPM and alternative to chitin synthesis inhibitors.

Quality by design (Qbd) assisted development of phytosomal gel of aloe vera extract for topical delivery.

The aim of the current study was to develop the phytosomal gel of aloe vera extract for improved topical delivery. Aloe vera extract loaded phytosomal system was developed by fixing the amount of aloe vera extract and ethanol and by varying the concentration of lecithin (0.15-0.25% w/v) and speed of rotation (80-120 rpm). Different formulation batches were prepared as per the Design expert software. A 22 Factorial design was applied to optimize the formulation on the basis of vesicular size and entrapment efficiency. Developed formulations were evaluated for vesicular size, entrapment efficiency, PDI, zeta potential and in-vitro release. Further stability studies were also performed. For the optimized formulation (F09), vesicular size, entrapment efficiency and PDI were found as 123.1 ± 1.44 nm, 95.67 ± 0.27% and 0.98 ± 0.06. Zeta potential of -11.9 mV and drug release of 56.91 ± 4.1% obtained in 24 h. Drug release kinetics from the phytosomes follows Higuchi model. TEM micrograph confirms the uniform structure of phytosomes. Phytosomal gel of optimized phytosomal formulation (F09) was developed with 1% Carbopol 934 and physically characterized on the basis of pH, viscosity, homogeneity and drug content. Ex-vivo permeation study showed the better permeation and flux profile of phytosomal gel with the conventional aloe vera extract gel. Also, studies on phytosomal formulation and gel showed stability up-to 3 months. Thus overall, it can be concluded that the phytosomal gel is a good carrier for topical delivery of herbal extract such as aloe vera.

A systematic review on phytochemicals for the treatment of dengue.

Dengue fever is prevalent in subtopic regions, producing mortality and morbidity worldwide, which have been of major concern to different governments and World Health Organization. The search of new anti-dengue agents from phytochemicals was assumed to be highly emergent in past. The phytochemicals have been used in wide distribution of vector ailments such as malaria. The demand of the phytochemicals is based on the medicines which are mostly considered to be safer, less harmful than synthetic drugs and nontoxic. This review mentions majorly about the phytochemicals potentially inhibiting dengue fever around the world. The phytochemicals have been isolated from different species, have potential for the treatment of dengue. Different crude extracts and essential oils obtained from different species showed a broad activity against different phytochemicals. The current studies showed that natural products represent a rich source of medicines toward the dengue fever. Furthermore, ethnobotanical surveys and laboratory investigation established identified natural plants species in the development of drug discovery to control the dengue fever.

Clinical Factors Affecting Bevacizumab Efficacy With and Without Conventional Chemotherapy in Metastatic Colon Cancer.

PURPOSE: Bevacizumab (BZ) combined with first line chemotherapy (CC) has shown good clinical outcomes in metastatic colorectal cancer (mCRC). Overall survival (OS) and/or progression free survival in mCRC patients receiving BZ with or without 5FU-based CC is thought to be affected by clinical and morphological factor(s). PATIENTS AND METHODS: We reviewed retrospective medical records of all consecutive mCRC patients treated with BZ with or without CC at tertiary care center between 2003 and 2009 out of which149 patients (m = 77, f = 72) were eligible. RESULTS: Our study population had a mean age at diagnosis of 63.5 years (SD = 11) with median follow-up period of 19.4 months. On initial radiological evaluation following BZ therapy, 56 patients (m = 31, f = 25) had complete or partial response categorized as "early responders." Remaining patients (m = 46, f = 47) who were either stable or showed progressive disease were categorized as "non-responders." Fifty percent among early responders and 60% among non-responders [relative risk (RR) 0.67 (95% confidence interval (CI), 0.43-1.06)] demonstrated disease progression on follow up. There was a slightly better OS among early responders compared to non-responders (median 21.5 months days versus 16.8 months, P = 0.07). Cox regression analysis suggested male sex (RR 0.65, 95% CI, 0.43-0.98), hematochezia (RR 0.63, 95% CI, 0.4-0.98), resectable primary tumor (RR 0.42, 95% CI, 0.24-0.72) and resectable metastatic mass (RR 0.32, 95% CI, 0.14-0.74) were found to be associated with longer OS. Abdominal pain (RR 1.76, 95% CI, 1.1-2.8), accompanying diabetes (RR 1.76, 95% CI, 1.09-2.85), and unexplained weight loss (RR 2.73, 95% CI, 1.73-4.29) were associated with poor OS. CONCLUSIONS: Better OS among mCRC patients with resectable primary and metastatic tumors was seen. This is the first study to demonstrate slightly better outcome in males and negative influence of diabetes on outcome in mCRC treated with BZ.

RNA interference-mediated knockdown of voltage-gated sodium channel (MpNav) gene causes mortality in peach-potato aphid, Myzus persicae.

Voltage-gated sodium channels (VGSC) are transmembrane proteins that generate an action potential in excitable cells and play an essential role in neuronal signaling. Since VGSCs play a crucial role in nerve transmission they have become primary targets for a broad range of commercial insecticides. RNA interference (RNAi) is a valuable reverse genetics tool used in functional genomics, but recently, it has also shown promise as a novel agent that could be used to control agricultural insect pests. In this study, we targeted the VGSC (MpNav) gene in the peach-potato aphid Myzus persicae, by oral feeding of artificial diets mixed with dsRNAs. Knock-down of MpNav gene expression caused up to 65% mortality in 3rd instar nymphs. Moreover, significantly lower fecundity and longevity was observed in adult aphids that had been fed with dsMpNav solution at the nymphal stage. Analysis of gene expression by qRT-PCR indicated that the aphid mortality rates and the lowered fecundity and longevity were attributable to the down-regulation of MpNav by RNAi. Taken together, our results show that MpNav is a viable candidate target gene for the development of an RNAi-based bio-aphicide.

Environmental enteropathy.

PURPOSE OF REVIEW: Environmental enteropathy has long been recognized as an important intermediary condition leading to chronic malnutrition in children in developing countries. Interest has lately renewed in this topic because of increased focus on improving the quality of lives as opposed to just saving them. Here, we provide an overview of recent scientific literature and our perspective about this disorder. RECENT FINDINGS: Current understanding of the disorder of environmental enteropathy is based on studies conducted decades ago. Results of some new studies on histopathologic characterization of environmental enteropathy are currently awaited. Given the challenges of diagnosing environmental enteropathy using the gold standard test of intestinal biopsy, different biomarkers have been tested as proxies of environmental enteropathy and eventually, chronic malnutrition. Available data fail to point toward a single ideal biomarker, though considerable work is still ongoing. A few interventional studies have also been conducted with improvement in environmental enteropathy as outcome. SUMMARY: The basic histopathology of environmental enteropathy has been defined previously, and more advanced analysis to study the pathophysiology of this disorder is currently being carried out. Many biomarkers, which represent the different mechanisms involved in environmental enteropathy, have been tested as proxies of environmental enteropathy. Although no single biomarker fits the description of an ideal biomarker yet, a few of the more promising biomarkers are being validated in different studies. Finally, the few interventions which have been tried to treat environmental enteropathy, thus far, are summarized.