Metabolomic Approach to Identify the Potential Metabolites from Alpinia malaccensis for Treating SARS-CoV-2 Infection.

The advent of the new coronavirus, leading to the SARS-CoV-2 pandemic, has presented a substantial worldwide health hazard since its inception in the latter part of 2019. The severity of the current pandemic is exacerbated by the occurrence of re-infection or co-infection with SARS-CoV-2. Hence, comprehending the molecular process underlying the pathophysiology of sepsis and discerning possible molecular targets for therapeutic intervention holds significant importance. For the first time, 31 metabolites were tentatively identified by GC-MS analysis from Alpinia malaccensis. On the other hand, five phenolic compounds were identified and quantified from the plant in HPLC-DAD analysis, including (-) epicatechin, rutin hydrate, rosmarinic acid, quercetin, and kaempferol. Nine GC-MS and five HPLC-identified metabolites had shown interactions with 45 and 30 COVID-19-associated human proteins, respectively. Among the proteins, PARP1, FN1, PRKCA, EGFR, ALDH2, AKR1C3, AHR, and IKBKB have been found as potential therapeutic targets to mitigate SARS-CoV-2 infection. KEGG pathway analysis also showed a strong association of FN1, EGFR, and IKBKB genes with SARS-CoV-2 viral replication and cytokine overexpression due to viral infection. Protein-protein interaction (PPI) analysis also showed that TP53, MMP9, FN1, EGFR, and NOS2 proteins are highly related to the genes involved in COVID-19 comorbidity. These proteins showed interaction with the plant phytoconstituents as well. As the study offers a robust network-based procedure for identifying biomolecules relevant to COVID-19 disease, A. malaccensis could be a good source of effective therapeutic agents against COVID-19 and related viral diseases.

Short-term Safety Performance Functions by Random Parameters Negative Binomial-Lindley model for Part-time Shoulder Use.

Part-time Shoulder Use (PTSU) is a traffic management and operation strategy that allows the use of the left or right shoulder as a travel lane, typically during the peak hours of the day. Though PTSU is an effective strategy for increasing roadway capacity in congested traffic conditions, there is very limited quantitative information about PTSU design elements and operational strategy in the existing literature, which could impact the occurrence of crashes on freeways. This study contributes to the safety literature by analyzing various potential crash contributing factors related to PTSU operation and design elements through the development of short-term Safety Performance Functions (SPFs). A comparison of the estimated models demonstrated that by utilizing the mixed distribution and allowing the posterior parameter estimates of explanatory variables to vary from one observation to another, the Random Parameters Negative Binomial-Lindley (RPNB-L) model outperformed the traditional NB and fixed coefficient NB-L models. The results of the proposed RPNB-L model indicated that the PTSU implemented sections experienced a lower number of traffic crashes compared to the non-PTSU freeway sections. Among the attributes related to PTSU operation and design elements, the usage of the leftmost shoulder lane as PTSU, the presence of emergency rest areas for damaged vehicles, and adequate shoulder width would significantly reduce crash frequency for the PTSU implemented freeways. Moreover, investigation of the identified hotspots revealed that the transition areas (start/end locations of PTSU) are the most critical sections. The findings from this research could assist transportation agencies to take appropriate countermeasures for preventing and reducing crash occurrences on PTSU implemented freeways.

Fimbristylis aestivalis Vahl: a potential source of cyclooxygenase-2 (COX-2) inhibitors.

Cyclooxygenase-2 (COX-2) is an inducible enzyme that accelerates the biosynthesis of PGs during inflammation and has emerged as an important therapeutic target for anti-inflammatory drugs. Natural compounds may serve as a source of inspiration for pharmaceutical chemists and a foundation for developing innovative COX-2 inhibitors with fewer side effects. Therefore, the objective of this study was to identify the potent COX-2 inhibitor and anti-inflammatory activity of the Fimbristylis aestivalis whole plant extract (FAWE). The plant extract was found dominant with rosmarinic acid followed by catechin hydrate, syringic acid, rutin hydrate, (-) epicatechin, quercetin, myricetin, and catechol. FAWE exhibited considerable dose-dependent analgesic efficacy in all analgesic test models. FAWE also showed promising anti-inflammatory potential in carrageenan-induced inflammations in mice. This result was corroborated by molecular docking, revealing that the aforesaid natural polyphenols adopt the same orientation as celecoxib in the COX-2 active site. On the other hand, molecular dynamics (MD) simulations were performed between the most abundant components (rosmarinic acid, catechin hydrate, and syringic acid) and COX-2. Based on hydrogen bonding, RMSD, RMSF, radius of gyration, PCA, and Gibbs free energy landscape analysis, the results demonstrated that these compounds are very stable in the active site of COX-2, indicating substantial COX-2 inhibitory activity.

Rutin hydrate and extract from Castanopsis tribuloides reduces pyrexia via inhibiting microsomal prostaglandin E synthase-1.

Castanopsis tribuloides belongs to the oak species (Fagaceae) and it is commonly distributed in evergreen forests of Bangladesh, India, Myanmar, Nepal, China, and Thailand. Our present study aimed at uncovering the antipyretic potential of methanol extract of C. tribuloides bark (CTB) in the mice models. Baker's yeast pyrexia model was employed to determine the antipyretic potentials of the extract. Besides, molecular docking and dynamics simulation of CTB phenolic compounds were explored to validate the experimental results and gain insight into the possible antipyretic mechanism of action that can lead to the design and discovery of novel drugs against mPGES-1. The results revealed that CTB (400 mg/kg) significantly inhibited (P < 0.001) the elevated body temperature of mice since 0.5 h, which is more prominent than the standard. At dose 200 mg/kg, the bark extract also produced significant (P < 0.05) antipyretic activity since 2 h. HPLC-DAD analysis identified and quantified nine polyphenolic compounds from the extract, including rutin hydrate, (-) epicatechin, caffeic acid, catechin hydrate, catechol, trans-ferulic acid, p-coumaric acid, vanillic acid, and rosmarinic acid. Molecular docking study suggested probable competition of these phenolic compounds with glutathione, an essential cofactor for microsomal prostaglandin E synthase-1 (mPGES-1) activity. Additionally, RMSF, RMSD, Rg, and hydrogen bonds performed during MD simulations revealed that rutin hydrate (rich in CTB) bound to the mPGES-1 active site in a stable manner and thus inactivating mPGES-1. Therefore, it can be concluded that rutin hydrate reduces pyrexia in mice via downregulating PGE2 synthesis by inhibiting mPGES-1 activity.

Phenolic compounds and extracts from Crotalaria calycina Schrank potentially alleviate pain and inflammation through inhibition of cyclooxygenase-2: An in vivo and molecular dynamics studies.

Crotalaria calycina Schrank is a local Bangladeshi plant well-accepted by the tribal population for its medicinal properties. The primary approach of our study was to uncover the analgesic and anti-inflammatory potential of methanol extract of C. calycina stem in mice model with in silico molecular docking and molecular dynamics simulation approach. Phenolic compounds were identified and quantified from the extract through high-performance liquid chromatography-diode array detector (HPLC-DAD) analysis. Writhing assay through injection of acetic acid, licking assay through formalin injection, and finally, hot plate assay was employed to observe the analgesic activity. The carrageenan-induced paw edema model was employed to determine the anti-inflammatory potential of the extract. In silico molecular docking and molecular dynamics were also run to validate the in vivo study results. Eight polyphenolic compounds from the extract were identified and quantified via HPLC-DAD analysis, and (-) epicatechin was most abundantly distributed (87.15 ± 0.24 mg/100 g dry extract). In vivo study revealed that 400 mg/kg dose significantly inhibited (P < 0.01) the writhing response in the writhing assay and demonstrated the highest percent of inhibition of licking (70.67%) in the late part of the licking test. The same extract dose produced the highest (74.71%) percent of maximal effect (% MPE) in the hot plate assay. It demonstrated the highest percent of edema inhibition (68.00%) in the fourth hour of the paw edema assay. Molecular docking and molecular dynamics simulation of (-) epicatechin, caffeic acid, and kaempferol with cyclooxygenase-2 revealed that they have similar interactions to the standard inhibitor celecoxib. These valuable bioactive compounds may induce significant analgesic and anti-inflammatory properties in MECCS. Therefore, based on the findings of this study, it can be concluded that C. calycina stem can be a prospect in the medicinal field due to its remarkable analgesic and anti-inflammatory effect.

Mechanical versus chemical pleurodesis for management of primary spontaneous pneumothorax evaluated with thoracic echography.

The current study is designed to compare the effectiveness of brushing the pleura vs. instillation of minocycline for the management of primary spontaneous pneumothorax, and to assess the sensitivity of echography in defining areas of defects. Blebectomy and pleurodesis were carried out thoracoscopically on 84 patients. In group A (42 patients), abrasions were induced using a sponge on a long ring forceps. Group B (42 patients) received intrapleural instillation of minocycline. Echography was carried out two weeks after discharge and then repeated two weeks later. Follow-up ranged between 28 and 39 months. Two patients were excluded from group A for incomplete follow-up. In group A, five patients (12%) showed areas of free mobility of the lung on first echography. At the second examination, three (7% of the total) showed the same areas of mobility; one patient developed an attack of localized pneumothorax after 32 and another after 45 weeks. Each had three adjacent areas of free mobility. In group B, two patients each showed one area of free mobility on the first and second examinations but no recurrence during follow-up. The two groups had comparable chest drainage, postoperative hospital stay and complication rates. The patients in group B demonstrated a trend towards a decreased rate of prolonged air leaks (2% vs. 5%; P=0.100). Thus, pleurodesis by instillation of minocycline as a part of thoracoscopy is more effective than brushing the pleura. Thoracic echography is a highly sensitive method for assessing the effectiveness of pleurodesis.

Caustic esophageal strictures in children: 30 years' experience.

Many children in developing countries continue to sustain caustic esophageal injures. The first line of treatment is dilatation, unless contraindicated, where 60% to 80% success rate is expected. In cases of failure, esophageal replacement is the only hope for achieving normal swallowing. Over the last 30 years, more than 850 cases of esophageal replacement were done in the Pediatric Surgery Department at Ain-Shams University. Three types of replacement were performed, gastric pull-up (75 cases), retrosternal colon replacement (550 cases), and, in the last 12 years, transhiatal esophagectomy with posterior mediastinal colon replacement (225 cases). Complications in the last 475 cases include 10% cervical leakage, 5% proximal strictures, 2% postoperative intestinal obstruction, 1% mortality, and 0.6% late graft stenosis. Colonic replacement of the esophagus is the ideal treatment in cases of caustic esophageal strictures after failure of dilatation. The posterior mediastinal route is shorter, and in long-term follow-up results show improved evacuation and less reflux than with the retrosternal route.