Effect of home-based pulmonary rehabilitation on exercise capacity in post COVID-19 patients: a randomized controlled trail.

BACKGROUND: Coronavirus 2019 (COVID-19) is an epidemic condition that compromises various consequences. The goal of this study was to investigate the effect of home-based pulmonary rehabilitation on exercise capacity in patients with post COVID-19 syndrome. METHODS: The study was designed as a randomized control trial. A total of sixty-eight patients with post COVID-19 syndrome complaining of fatigue, dyspnea, and exercise intolerance participated in this study. Their ages ranged from 40 to 70 years old. The patients were randomly classified into two equal groups. The control group received usual medical care only, whereas the rehabilitation group received a selected home-based pulmonary rehabilitation exercise program plus the same usual medical care. The Physical Fitness Index (PFI), Chalder fatigue index, SF-36 questionnaire, dyspnea scale, and six-minute walk test (6 MWT) were measured before and after 12 weeks of intervention. RESULTS: The rehabilitation group showed a significant lower mean of Chalder fatigue (11.1 ± 0.94) and a higher mean of 6MWT (439.7 ± 25.3) and PFI (52.3 ± 10.2), in addition to a higher mean of the SF-36 Questionnaire (66.4 ± 3.7) and a significant improvement of dyspnea in the mMRC score (26.7%), grade 2, (63.3%), grade 1 (10%), and grade 0 with a p-value < 0.001 when compared to the control group. CONCLUSION: Home-based pulmonary rehabilitation (HBPR) for patients with post COVID-19 syndrome is effective and has a potential direct influence on exercise capacity, fatigue, dyspnea, and quality of life. HBPR could be considered an adjunctive, applicable, and low-cost therapy for patients with post COVID-19 syndrome. TRIAL REGISTRATION: The study was registered in Pan African Clinical Trial Registry as a clinical trial ID (PACTR202111640499636), November 2021.

Bioethanol Production from Characterized Pre-treated Sugarcane Trash and Jatropha Agrowastes.

Low production costs and a potential feedstock supply make lignocellulosic ethanol (bioethanol) an important source of advanced biofuels. The physical and chemical preparation of this kind of lignocellulosic feedstock led to a high ethanol yield. In order to increase the yield of fermentable sugars, pretreatment is an essential process step that alters the lignocellulosic structure and improves its accessibility for the expensive hydrolytic enzymes. In this context, the chemical composition of sugarcane trash (dry leaves, green leaves, and tops) and jatropha (shell and seed cake) was determined to be mainly cellulose, hemicellulose, and lignin. Hydrogen peroxide and sodium hydroxide were applied in an attempt to facilitate the solubilization of lignin and hemicelluloses in five agrowastes. The extraction of hydrogen peroxide was much better than that of sodium hydroxide. A comparative study was done using SEM, EDXA, and FTIR to evaluate the difference between the two methods. The pretreated wastes were subjected to saccharification by commercial cellulases (30 IU/g substrate). The obtained glucose was fortified with nutrients and fermented statically by Saccharomyces cerevisiae F-307 for bioethanol production. The results revealed the bioethanol yields were 325.4, 310.8, 282.9, 302.4 and 264.0 mg ethanol/g treated agrowastes from green leaves of sugarcane, jatropha deolied seed cake, tops sugarcane, dry leaves of sugarcane, and jatropha shell, respectively. This study emphasizes the value of lignocellulosic agricultural waste as a resource for the production of biofuels as well as the significance of the extraction process.

Enhancement of Vitamin C's Protective Effect against Thimerosal-Induced Neurotoxicity in the Cerebral Cortex of Wistar Albino Rats: An In Vivo and Computational Study.

Vitamin C was examined to ameliorate the neurotoxicity of thimerosal (THIM) in an animal model (Wistar albino rats). In our work, oxidative and antioxidative biomarkers such as SOD, LPO, and GSH were investigated at various doses of THIM with or without concurrent vitamin C administration. Furthermore, the adverse effects of THIM on hepatic tissue and cerebral cortex morphology were examined in the absence or presence of associated vitamin C administration. Also, we studied the effect of vitamin C on the metallothionein isoforms (MT-1, MT-2, and MT-3) in silico and in vivo using the RT-PCR assay. The results showed that the antioxidant biomarker was reduced as the THIM dose was raised and vice versa. THIM-associated vitamin C reduced the adverse effects of the THIM dose. The computation studies demonstrated that vitamin C has a lower ΔG of -4.9 kcal/mol compared to -4.1 kcal/mol for THIM to bind to the MT-2 protein, which demonstrated that vitamin C has a greater ability to bind with MT-2 than THIM. This is due to multiple hydrogen bonds that exist between vitamin C and MT-2 residues Lys31, Gln23, Cys24, and Cys29, and the sodium ion represents key stabilizing interactions. Hydrogen bonds involve electrostatic interactions between hydrogen atom donors (e.g., hydroxyl groups) and acceptors (e.g., carbonyl oxygens). The distances between heavy atoms are typically 2.5-3.5 Å. H-bonds provide directed, high-affinity interactions to anchor the ligand to the binding site. The five H-bonds formed by vitamin C allow it to form a stable complex with MT, while THIM can form two H-bonds with Gln23 and Cys24. This provides less stabilization in the binding pocket, contributing to the lower affinity compared to vitamin C. The histopathological morphologies in hepatic tissue displayed an expansion in the portal tract and the hepatocytes surrounding the portal tract, including apoptosis, binucleation, and karyomegaly. The histopathological morphologies in the brain tissue revealed a significant decrease in the number of Purkinje cells due to THIM toxicity. Interestingly, THIM toxicity was associated with hemorrhage and astrogliosis. Both intracellular and vasogenic edema appeared as the concentrations of THIM rose. Finally, vitamin C ameliorated the adverse effect on the cerebral cortex in Wistar albino rats.

Synergistic Differential DNA Demethylation Activity of Danshensu (Salvia miltiorrhiza) Associated with Different Probiotics in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a major hepatic disorder occurring in non-alcohol-drinking individuals. Salvianic acid A or Danshensu (DSS, 3-(3, 4-dihydroxyphenyl)-(2R)-lactic acid), derived from the root of Danshen (Salvia miltiorrhiza), has demonstrated heart and liver protective properties. In this work, we investigated the antioxidant activity and hepatoprotective activity of Danshensu alone and in combination with different agents, such as probiotic bacteria (Lactobacillus casei and Lactobacillus acidophilus), against several assays. The inhibition mechanism of the methylation gene biomarkers, such as DNMT-1, MS, STAT-3, and TET-1, against DSS was evaluated by molecular docking and RT-PCR techniques. The physicochemical and pharmacokinetic ADMET properties of DSS were determined by SwissADME and pkCSM. The results indicated that all lipid blood test profiles, including cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), were reduced after the oral administration of Danshensu combined with probiotics (L. casei and L. acidophilus) that demonstrated good, efficient free radical scavenging activity, measured using anti-oxidant assays. ADMET and drug-likeness properties certify that the DSS could be utilized as a feasible drug since DSS showed satisfactory physicochemical and pharmacokinetic ADMET properties.

CT volumetry study of microfat graft survival from different donor sites in augmenting the enophthalmic socket.

PURPOSE: To evaluate autologous fat grafts harvested from the abdomen versus the thigh for treating the enophthalmic socket using CT volumetry. METHODS: A randomized prospective interventional study including 20 patients suffering from unilateral enophthalmic socket. Pre-operative clinical assessment included photographs, exophthalmometry reading as well as CT volumetry for volume deficit calculations and the harvesting site was randomly allocated (abdomen or thigh). All patients completed 6 months of follow-up. Exophthalmometry change and percentage of retained fat with the globe included and without it at follow-up were measured. RESULTS: Microfat graft survival showed no statistically significant correlation with sex, age, or donor site. Mean percentage of retained fat with globe and without it were 14.75% and 25.31%, respectively. Difficulty of extraction and degree of volume deficit correlated significantly with percentage of fat retained. Exophthalmometer change correlated significantly with percentage of fat retained. CONCLUSION: Autologous fat grafting is a safe and effective technique for volume augmentation of enophthalmic sockets regardless of its harvesting site. CT volumetry has an important role in accurately measuring the volume deficit as well as the postoperative results.

Effect of different types of aerobic training on peak VO2 and ejection fraction for diastolic heart failure patients; a comparative randomized control trial.

BACKGROUND: Heart failure is described by a lack of confirmed efficient therapies and exercise intolerance. Engagement in physical activity decreases the possibility of adverse cardiovascular consequences involving heart failure. THE PURPOSE OF THE STUDY: Determine the effect of different types of aerobic training on peak VO2 and ejection fraction in diastolic heart failure patients. SUBJECT AND METHODS: The study was designed as a randomized control trail. Forty-eight eligible male patients with diastolic heart failure, aged between 50 and 65 years old, enrolled in this study. They were picked up from Police hospital outpatient clinic and were assigned to 2 equal groups in numbers. The first group (A) received aerobic exercise for the upper limb in the form of arm ergometer exercises, while the second group (B) received aerobic exercise for the lower limb in the form of cycling. Training duration for both groups was 3 sessions/week for 12 weeks. Peak VO2, and ejection fraction of both groups were measured and compared pre- and post-treatment. RESULTS: There was no significant difference (p > 0.05) in the ejection fraction between groups post-treatment. However, a significant increase (p < 0.001) was observed in the peak VO2 of group B when compared to group A post-treatment. CONCLUSION: There is no effect of different types of aerobic training on ejection fraction in diastolic heart failure patients, but lower limb exercise is more effective than upper limb exercise in improving peak VO2 in diastolic heart failure patients. Therefore, the current study recommended the use of lower limb exercise over upper limb exercise in training diastolic heart failure patients. CLINICAL TRIAL REGISTRATION: The study was registered in ClinicalTrial.gov as a clinical trial ID (NCT05637125).

Histopathology and electron microscopy evaluation of the sildenafil effect on diabetic rats' retinae.

PURPOSE: Although there is increasing evidence that phosphodiesterase-5 (PDE-5) inhibitors modify the effect of diabetes on different tissues, its effect on diabetic retinopathy is not well studied. METHODS: Forty male Sprague-Dawley (SD) rats were divided into four groups: group I = control group that received no treatment; group II (diabetic group), in which diabetes was induced by a single streptozotocin injection; group III (sildenafil small dose, SSD), in which diabetes was similarly introduced (however, rats received daily oral 1 mg/kg sildenafil citrate (SC) for 3 months); and group IV (sildenafil large dose, SLD), which was as in group 3, but SC was 2.5 mg/kg. After 3 months, globes were removed and retinae were dissected; one globe from each rat was examined by light microscopy (LM), and the other by electron microscopy (EM). RESULTS: In contrast to the control group, diabetic rats in group II demonstrated well-established diabetic changes in the form of capillary congestion, decreased cell population, hyaline changes of capillary walls, and degenerated nerve fiber layer by LM. Similarly, EM demonstrated photoreceptor degeneration, mitochondrial cristolysis, and vacuolated depleted cells among other features in group II. These diabetic features were less prominent in group III and nearly absent in group IV. CONCLUSION: SC use in the early stages of DR may prevent/delay diabetic retinopathy development or progression in diabetic rat models, an effect that seems to be dose-related.

Effect of high-intensity laser therapy versus shockwave therapy on selected outcome measures in osteoporotic long-term hemiparetic patients: a randomized control trial.

BACKGROUND: This study aimed to compare the effects of high-intensity laser therapy (HILT) and extracorporeal shock wave therapy (ESWT) in treating consequences of osteoporosis in hemiparetic patients. METHODS: A randomized controlled trial was conducted on hemiplegic patients with osteoporosis. They were randomly classified into three equal groups (n = 40 in each group). The control group received medication and traditional physiotherapy programs for stroke patients. The high-intensity laser (HIL) group received the same intervention as the control group in addition to high-intensity laser therapy. The shock wave (SW) group received the same intervention as the control group in addition to shock wave therapy. The three groups received an intervention that lasted 3 sessions/week for 12 weeks). All groups were assessed before and after therapy for the degree of pain, fall risk, and quality of life. RESULTS: A statistically significant difference (p < 0.05) was found concerning VAS, which had a significant difference in favor of HILT and ESWT groups compared to the control group; however, no significant difference was determined between HIL and SW groups. Regarding the overall stability index, SFBBS, and QUALEFFO-41, there was a significant difference in favor of HIL and SW groups compared to the control group, and a significant difference was found in HIL when compared to SW. CONCLUSION: The current study indicates that the combined traditional physical therapy and HILT and ESWT have clinical significance in improving osteoporotic long-term hemiparetic patients with more favor to HILT. TRIAL REGISTRATION: The study was registered as a clinical trial at ClinicalTrial.gov ID (NCT05616611).

Protective Action Mechanisms of Launaea mucronata Extract and Its Nano-Formulation against Nephrotoxicity in Rats as Revealed via Biochemical, Histopathological, and UPLC-QTOF-MS/MS Analyses.

Plants belonging to the Launaea genus have been extensively utilized ethnopharmacologically to treat a variety of diseases, including kidney disorders. Chromium is a common industrial pollutant that has been linked to kidney disease. The present work was designed for the investigation of the UPLC-QTOF-MS/MS metabolite profile of the L. mucronate ethanolic extract (LME), along with assessing the mechanistic protective actions of LME and its nano-silver formulation (LMNS) against K2Cr2O7-induced nephrotoxicity in rats. LMNE was successfully biosynthesized and confirmed using UV-Visible (UV-Vis) spectroscopy and transmission electron microscopy (TEM). The nephroprotective effects of LME and LMNE was assessed in rats exposed to potassium dichromate (K2Cr2O7, 15 mg/kg BW) to cause nephrotoxicity. LME and LMNS, separately, were administered twice daily for 14 days at doses of 200 and 400 mg/kg BW, respectively. The kidney function, catalase, UGT, Nrf2, PGE2, Cox-2, ERK, and MAPK levels in renal tissue were all assessed, along with histopathological examinations for exploring their ameliorative effects. Forty-five bioactive metabolites were annotated belonging to flavonoids, phenolic and organic acids, coumarins, and fatty acids. Metabolite profiling revealed that chlorogenic acid, apigenin, and luteolin glycosides were the main phenolics, with chlorogenic acid-O-hexoside reported for the first time in LME. The findings revealed that the serum kidney function indicators (urea and creatinine) were markedly elevated in K2Cr2O7-intoxicated rats. Furthermore, inflammatory indicators (COX-2 and PGE2), MAPK, and ERK were all markedly elevated in kidney tissue, whereas catalase, UGT, and Nrf2 levels were downregulated. Histological and immunohistochemical assays confirmed the toxic effects of K2Cr2O7 in the kidneys. In contrast, the administration of LME and LMNS prior to K2Cr2O7 considerably improved the architecture of the renal tissue, while also restoring levels of most biochemical markers. Functioning via the inhibition of the MAPK/ERK pathway, activating Nrf2, and modifying the antioxidant and metabolic enzymes, LME and LMNS exerted their nephroprotective effects against K2Cr2O7-induced toxicity.

Enhancement of the quality attributes and health benefits synbiotic yoghurt from cow's milk.

The present work delighted on extraction of galactomannan polysaccharide from guar gum beans and microbial galactomannan source. Effect of replacing non-fat dry milk that used to fortify cow's milk in yoghurt industry with the two extracted galactomannans and commercial galactomannan as food additives was studied. Control yoghurt treatment was made from 3.0% fat cow's milk that was fortified with 1.5% non-fat dry milk. Another 6 yoghurt treatmentwas fortified with 0.15, 0.25% of commercial, guar and microbial galactomannan respectively. All treatments were cultured with the probiotic starter (1.0% Streptococcus thermophilus + 1.0% Lactobacillus delbrueckii subsp. Bulgaricus + 1.0% Bifidobacteriumbifidum). The obtained results indicated that yoghurt supplementation with the three types of galactomannans increased the acidity, curd tension, total solids content, decreased pH values and syneresis of yoghurt treatments. Control yoghurt and commercial galactomannan yoghurt were not significantly different from the corresponding batches those made with either guar galactomannan and microbial galactomannan in fat, protein and ash content. Yoghurt treatments which supplemented with the three types of galactomannans have higher bifidobacteria counts and organoleptic scores than the control treatment yoghurt.

Effect of electromagnetic therapy versus low-level laser therapy on diabetic patients with trigeminal neuralgia: a randomized control trial.

BACKGROUND: Trigeminal neuralgia (TN) is defined as intense, abrupt, often unilateral, stabbing, short, repeated episodes of pain in one or more distributional branches of the trigeminal nerve. AIM: To see how electromagnetic therapy (EMT) compared to low-level laser therapy (LLLT) affect TN in diabetes patients. DESIGN: This is a randomized controlled trial. SETTING: Physical therapy and Neurology Outpatients Clinics at Faculty of Physical Therapy. POPULATION: One hundred and forty diabetic patients with TN were evaluated for eligibility. As a result, 126 diabetic patients with TN were included in this trial. They were randomly divided into three equal-sized groups using random allocation software. Due to travel to another country, two patients did not complete the treatment protocol, and four opted out of the post-therapy evaluation. So, 120 volunteer diabetic patients with TN of both sexes were diagnosed for the participation in this study by a neurologist (N.=40 in each group). METHODS: For two months, participants in the control group A received the medication only (oral hypoglycemic drugs, Analgesics, vitamin B12), participants in the study group B received the medications as in group A in addition to LLLT, and participants in the study group C received medication as in group A in addition to electromagnetic therapy (EMT). The primary outcome was the amplitude of compound muscle action potentials of temporalis and masseter muscles by using NEXUS 10 (Mind media). The secondary outcome was pain intensity by using the Visual Analog Scale (VAS). RESULTS: According to the results of this study, there is a statistically significant difference in visual analog scale scores and the amplitude of compound muscle action potentials of the temporalis and masseter muscles among groups in favor of group B. CONCLUSIONS: After treatment, all groups improved significantly, with the laser group outperforming the electromagnetic group by a large margin. For irradiation, LLLT was more effective than EMT in reducing diabetic patients' trigeminal pain, and increasing masseter and temporalis muscles compound action potential amplitude in diabetic patients with TN. CLINICAL REHABILITATION IMPACT: LLLT was more effective than EMT at reducing diabetic patient's trigeminal pain, and increasing masseter and temporalis muscles compound action potential amplitude in diabetic patients with TN patients after two months of interventions.

Novel naringin tablet formulations of agro-resides based nano/micro crystalline cellulose with neuroprotective and Alzheimer ameliorative potentials.

This study aimed to prepare micro/nanocrystalline cellulose-loaded naringin (NAR) tablets and evaluate their neuro-protective/therapeutic potentials in Alzheimer's disease (AD) model. Micro/nanocellulose was prepared from different agro-wastes, and the different cellulose preparations were then used to formulate eight oral tablets of naringin micro/nanoparticles by direct compression. AD-like symptoms were induced in adult male Sprague Dawley rats by co-administration of 150 mg/kg AlCl3 and 300 mg/kg D-galactose (oral administration/one week), and NAR tablets were assessed for neuroprotective/therapeutic potentials in terms of behavioral changes, levels of neurodegenerative and inflammatory markers, brain redox status, neurotransmitter tones, and cortex/hippocampus histopathological alterations. NAR treatments have significantly reversed the neurotoxic effect of AlCl3 as demonstrated by improved spatial and cognitive memory functions and promoted antioxidant defense mechanisms in treated AD animals. Also, the neurodegeneration was markedly restrained as reflected by marked histopathological enhancement, and prevention/amelioration of neuropsychiatric disorders, besides the restorative effect on dysregulated neurotransmitters tone. Both NAR tablet forms showed an overall higher ameliorative effect compared to the DPZ reference drug. The formulated tablets represent promising neuroprotective/therapeutic agents for Alzheimer's disease.

Metabolomics approach of Symphyotrichum squamatum ethanol extract and its nano-Ag formulation protective effect on gastric ulcer via bio-chemical and pathological analyses.

ContextGastric ulcer (GU) a widely distributed ailment is associated with many causes, including alcohol consumption.Materials and MethodsChemical profiling of Symphyotrichum squamatum ethanol extract (SSEE) was established via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) and employed in a silver nano-formulation (SSEE-N-Ag). SSEE and SSEE-N-Ag antiulcer activities were estimated against ethanol-induced rats by biochemical, histological, and metabolomics assessments. Reduced glutathione, total antioxidant capacity and prostaglandin E2 levels and gastric mucosa histopathological examination were analysed. The rats' metabolome changing alongside action pathways were elucidated via metabolite profile coupled to multivariate data analysis.ResultsUPLC-MS profiling of SSEE identified 75 components belonging to various classes. Compared with control, EtOH-treated rats showed decreased of tissue GSH, TAC and PGE2 by 62.32%, 51.85% and 47.03% respectively. SSEE and SSEE-N-Ag administration mitigated biochemical and histopathological alterations. Serum metabolomics analysis revealed for changes in several low molecular weight metabolites with ulcer development. These metabolites levels were restored to normal post-administration of SSEE-N-Ag. SSEE-N-Ag as mediated via modulating numerous metabolic pathways such as lipids, pyrimidine, energy metabolism and phosphatidylinositol signalling. This study provides novel insight for metabolic mechanisms underlying gastric ulcer relieving effect.ConclusionPresent results revealed potential antiulcer effect of SSEE and SSEE-N-Ag by decreasing ulcer-associated syndromes, supporting their anti-ulcerogenic action.

Visual and Topographic Outcomes of Corneal Collagen Cross Linking for Post LASIK Ectasia.

Purpose: To assess the topographic and visual outcomes of corneal cross-linking (CXL) for post-LASIK ectasia. Methods: A retrospective case series of patients who had progressive post-LASIK ectasia, with at least 2 years of follow-up. They had epithelium-off CXL. Topographical and visual changes were recorded. Results: The study included 21 eyes of 11 patients. At month 24, the final logMAR corrected distance visual acuity (CDVA) and spherical equivalent (SE) were stable compared to baseline (0.16, and -2.0 diopter (D), respectively). The final Kmean and Kmax were 42.5 and 47.4 D, respectively. Stability or improvement in CDVA, SE, and Kmax was seen in 17 eyes (81%). Significant corneal thinning was seen (438 vs 457 microns, p = 0.003). Thinning by 2% or more was seen in 12 eyes (57.1%). Failure of CXL was seen in 4 eyes (19%). No other ocular complications were seen. Conclusion: CXL for post LASIK ectasia is a safe and effective modality. Despite corneal thinning, there was stability or improvement in topographic parameters and CDVA over the 2-year follow-up period.

Vaccine production and supply need a paradigm change.

We discuss the impact of COVID-19, the journey towards developing vaccines against the disease, and how biomanufacturing should evolve in order to meet similar challenges in the future.

Cytoprotective potentialities of carvacrol and its nanoemulsion against cisplatin-induced nephrotoxicity in rats: development of nano-encasulation form.

Cisplatin (Cisp) is a widely distributed chemotherapeutic drug for cancers. Nephrotoxicity is one of the most common side effects of the use of this drug. Carvacrol (CV) is a common natural compound in essential oils and extracts of medicinal plants with potent in vivo and in vitro bioactivities. The work was extended to achieve the target of investigation of the protective potentialities of CV and its nanoemulsion as a cytoprotective drug against Cisp-induced nephrotoxicity in albino rats. CV-nanoemulsion was prepared by a hydrophilic surfactant polysorbate 80 (Tween 80) and deionized water. The TEM image of the particle distribution prepared nanoemulsion is mainly spherical in shape with particle size varying between 14 and 30 nm. Additionally, the Cisp administration caused the increasing of the levels of urea and creatinine in the blood and serum. These increasing of urea and creatinine levels caused consequently the turbulence of the oxidative stress as well as the rising of hs-CRP, IL-6, and TNF-α levels in the serum. Also, histopathological changes of the kidney tissue were observed. These changes back to normal by treatment with CV-nanoemulsion. Expression levels of nephrotoxicity-related genes including LGALS3, VEGF, and CAV1 in kidney tissue using qRT-PCR were measured. The results revealed that the expression of LGALS3, VEGF and CAV1 genes was highly significantly increased in only Cisp treated group when compared with other treated groups. While, these genes expressions were significantly decreased in Cisp + CV treated group when compared with Cisp treated rats (P < 0.001). In addition, there were no significant differences between Cisp + nano-CV treated group and both negative control and nanoemulsion alone groups but it was not significant. In addition, the Western blot of protein analysis results showed that the LGALS3 and CAV1 are highly expressed only in Cisp + CV treated group compared with other groups. There was no significant difference between Cisp + nano-CV treated animals and negative control for both mRNA and protein expression. Based on these results, CV was combined with calcium alginate; a more stable capsule is formed, allowing for the formation of a double wall in the microcapsule. These results supported the therapeutic effect of CV and its nano-emulsion as cytoprotective agents against Cisp nephrotoxicity.

Immunomodulation of T- and NK-cell Responses by a Bispecific Antibody Targeting CD28 Homolog and PD-L1.

Checkpoint blockade therapies targeting PD-1/PD-L1 and CTLA-4 are clinically successful but also evoke adverse events due to systemic T-cell activation. We engineered a bispecific, mAb targeting CD28 homolog (CD28H), a newly identified B7 family receptor that is constitutively expressed on T and natural killer (NK) cells, with a PD-L1 antibody to potentiate tumor-specific immune responses. The bispecific antibody led to T-cell costimulation, induced NK-cell cytotoxicity of PD-L1-expressing tumor cells, and activated tissue-resident memory CD8+ T cells. Mechanistically, the CD28H agonistic arm of the bispecific antibody reduced PD-L1/PD-1-induced SHP2 phosphorylation while simultaneously augmenting T-cell receptor signaling by activating the MAPK and AKT pathways. This bispecific approach could be used to target multiple immune cells, including CD8+ T cells, tissue-resident memory T cells, and NK cells, in a tumor-specific manner that may lead to induction of durable, therapeutic antitumor responses.

Oral and Topical Anti-Inflammatory and Antipyretic Potentialities of Araucaria bidiwillii Shoot Essential Oil and Its Nanoemulsion in Relation to Chemical Composition.

Different parts of Araucaria bidiwillii (bunya pin) trees, such as nuts, seeds, bark, and shoots, are widely used in cooking, tea, and traditional medicines around the world. The shoots essential oil (EO) has not yet been studied. Herein, the chemical profile of A. bidiwillii shoots EO (ABSEO) was created by GC-MS analysis. Additionally, the in vivo oral and topical anti-inflammatory effect against carrageenan-induced models, as well as antipyretic potentiality of ABSEO and its nanoemulsion were evaluated. Forty-three terpenoid components were identified and categorized as mono- (42.94%), sesqui- (31.66%), and diterpenes (23.74%). The main compounds of the ABSEO were beyerene (20.81%), α-pinene (16.21%), D-limonene (14.22%), germacrene D (6.69%), ß-humulene (4.14%), and sabinene (4.12%). The ABSEO and its nanoemulsion exhibited significant inflammation suppression in carrageenan-induced rat paw edema model, in both oral (50 and 100 mg/kg) and topical (5% in soyabean oil) routes, compared to the control and reference drugs groups. All the results demonstrated the significant inflammation reduction via the inflammatory cytokines (IL-1ß and IL8), nitrosative (NO), and prostaglandin E2 (PGE2) supported by the histopathological studies and immunohistochemical assessment of MMP-9 and NF-κß levels in paw tissues. Moreover, the oral administration of ABSEO and its nanoemulsion (50 and 100 mg/kg) exhibited antipyretic activity in rats, demonstrated by the inhibition of hyperthermia induced by intramuscular injection of brewer's yeast. These findings advised that the use of ABSEO and its nanoemulsion against numerous inflammatory and hyperthermia ailments that could be attributed to its active constituents.

Renoprotective and therapeutic effects of newly water, ethanol, and butanol ginseng fractions in hypertensive and chronic kidney disease with L-NAME.

The present study investigated the protective and treatment effects of different ginseng fractions against L-NAME-induced renal toxicity in rats. The data obtained demonstrated that L-NAME significantly increased creatinine, urea, KIM-1, and lipocalin-2 levels in serum; and also increased renal MDA and eNOS levels compared with the control group. Three bioactive fractions were newly extracted from ginseng, analyzed by GC-MS analysis, and were examined for antimicrobial, prebiotic, and histological activities. All ginseng fractions improved such histological changes, as reflected by significant reductions in creatinine, urea, KIM-1, and LCN-2 levels in serum, and renal MDA and eNOS contents in tissue homogenate. The water ginseng fraction (WGF) has the highest prebiotic index of 4.7 toward Lactobacillus reuteri, and can improve the renal functions more than butanol ginseng fraction (BGF) and ethanol ginseng fraction (EGF). These three ginseng fractions significantly reversed L-NAME-induced depletion in the TNF-α gene expression level. Interestingly, WGF was able to improve the renal functions more than BGF and EGF. L-NAME led to alterations in the histological structure and functions of renal tissue of rats and ginseng supplementation could offer greater protection against these changes. Moreover, the WGF exhibited superior renoprotection properties when compared with the other two fractions: BGF and EGF, and the reference drug losartan.

Mean macular intercapillary area in eyes with diabetic macular oedema after anti-vascular endothelial growth factor therapy and its association with treatment response.

BACKGROUND: To evaluate the changes in the mean macular intercapillary area (ICA) from sequential enface optical coherence tomography angiography (OCTA) images following intravitreal anti-vascular endothelial growth factor (VEGF) therapy in initially treatment-naïve eyes with diabetic macular oedema (DME). METHODS: In this multicentre retrospective study, 6 × 6 and 3 × 3 mm customised, total retinal projection enface OCTA images were collected and processed for quantitative assessment of ICA by a customised MATLAB software. Measurements were done in concentric regions centred on the fovea-with the exclusion of foveal avascular zone (FAZ)-in 0.5 mm diameter increments as well as within the intervening rings. RESULTS: In this study, 6 × 6 mm OCTA images from 46 eyes of 29 patients, and 3 × 3 mm OCTA images from 23 eyes of 15 patients were included. There was no significant change in mean ICA after treatment in either scan size or in any measurement regions (all p > 0.05). Multivariate analysis revealed that baseline BCVA was significantly correlated with the visual outcome (p = 0.039). Additionally, after correction for age, baseline central retinal thickness (CRT), baseline BCVA, and retinopathy severity, mean ICA in the 1.5 mm circle was found to be a significant predictor of post treatment CRT, (p = 0.006). CONCLUSIONS: Absence of significant change in mean ICA after a minimum of three intravitreal anti-VEGF injections, may indicate that, in the short term, anti-VEGF injections neither impair nor improve macular perfusion in DME. Baseline BCVA was found to be a robust predictor of functional outcome, while inner mean ICA was a significant predictor for macular thickness outcomes.