Clinical behavior and survival of endodontically treated teeth with or without post placement: a systematic review and meta-analysis.

PURPOSE: Non-vital teeth usually exhibit substantial loss of coronal and radicular tooth structure, and use of posts after root canal treatment is controversial. This review examined whether placement of posts influences clinical behavior and survival probability of endodontically treated teeth (ETT). METHODS: An electronic search, without time restrictions, for publications written in English was undertaken in PubMed, Scopus, and Web of Science. Terms related to four main components (endodontically treated teeth, fixed prosthesis, post restoration, and survival rate) were used for the database search strategies. RESULTS: 57 studies met the inclusion criteria and were included in the qualitative analysis. Of the publications chosen for qualitative analysis, 17 clinical studies (11 prospective and 6 retrospective studies) were found to be suitable for quantitative analysis. These studies included 7,278 patients (7,330 ETT), with a mean age ± standard deviation (SD) of 45.46 ± 12.1 years. There was a statistically significant difference in survival rate between ETT with or without posts (P < 0.001). CONCLUSION: As compared with teeth with no posts, post placement on ETT may improve clinical performance and survival probability of endodontically treated teeth.

Machine learning assessment of vildagliptin and linagliptin effectiveness in type 2 diabetes: Predictors of glycemic control.

OBJECTIVE: Differential effects of linagliptin and vildagliptin may help us personalize treatment for Type 2 Diabetes Mellitus (T2DM). The current study compares the effect of these drugs on glycated hemoglobin (HbA1c) in an artificial neural network (ANN) model. METHODS: Patients with T2DM who received either vildagliptin or linagliptin, with predefined exclusion criteria, qualified for the study. Two input variable datasets were constructed: with or without imputation for missing values. The primary outcome was HbA1c readings between 3 to 12 months or the reduction in HbA1c levels. RESULTS: The cohort comprised 191 individuals (92 vildagliptin and 99 linagliptin). Linagliptin group had significantly higher disease burden. For imputed dataset, HbA1c was lower with linagliptin at 3 to 12 months (7.442 ± 0.408 vs. 7.626 ± 0.408, P < 0.001). However, there was a small yet significant difference in HbA1c reduction favoring vildagliptin over linagliptin (-1.123 ± 0.033 vs. -1.111 ± 0.043, P < 0.001). LDL level, uric acid, and the drug group were identified as predictors for HbA1c levels. In the non-imputed dataset HbA1c at 3 to 12 months was lower with linagliptin (median ± IQR: 7.489 ± 0.467 vs. 7.634 ± 0.467, P-value < 0.001). However, both linagliptin and vildagliptin exhibited similar reductions in HbA1c levels (both median ± IQR of -1.07 ± 0.02). Predictors for HbA1c levels included eGFR level and the drug group. CONCLUSION: Linagliptin effectively lowers HbA1c levels more than vildagliptin including in patients with comorbidities. DPP4-I choice is a constant predictor of HbA1c in all models.

Rate and Causes of Unplanned Hospital Returns within 60 Days following Head and Neck Surgery.

Introduction Unplanned hospital returns are frequent and may be preventable. Objective To comprehend the reasons for unplanned hospital readmission and return to the Outpatient Department (OPD) and Emergency Department (ED) within 60 days after discharge following head and neck surgery (HNS) at a tertiary care center in Saudi Arabia. Methods In the present retrospective study, the medical records of all patients who underwent HNS for benign and malignant conditions between January 2015 and June 2022 were reviewed in terms of demographic data, comorbidities, and reasons for hospital return. Results Out of 1,030 cases, 119 (11.55%) returned to the hospital within 60 days after discharge, 19 of which (1.84%) were readmitted. In total, 90 (8.74%) patients returned to the OPD, and 29 (2.82%), to the ED. The common reasons for readmission included infections (26.32%) and neurological symptoms (21.05%). For OPD visits, the common causes were hematoma (20%) and neurological symptoms (14.44%). For ED returns, the frequent causes were neurological symptoms (20.69%) and equipment issues (17.24%). Compared with nonreadmitted patients, readmitted patients had a higher preoperative baseline health burden when examined using the American Society of Anesthesiologists (ASA) score ( p = 0.004) and the Cumulative Illness Rating Scale (CIRS; p = 0.002). Conclusion The 60-day rates of unplanned hospital return to the OPD and ED were of 8.74% and 2.82% respectively, and 1.84% of the patients were readmitted. Hematoma, infections, and neurological symptoms were common causes. Addressing the common reasons may be beneficial to decrease postoperative hospital visits.

The impact of weekly semaglutide, a glucagon-like peptide-1 agonist, on kidney outcomes in adults with type 2 diabetes mellitus.

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with kidney complications. This study aims to investigate the effects of weekly subcutaneous semaglutide, a GLP-1 agonist, on kidney outcomes. Methods: This retrospective cohort study was conducted in nephrology and endocrinology clinics at KFAFH from March 2022 to February 2023. The sample size was determined based on hospital records, and randomly selected patients who met the inclusion criteria were included. The inclusion criteria included adults with T2DM who were on weekly subcutaneous semaglutide for 6 months or longer. Patients with type 1 diabetes mellitus, pregnant or gestational diabetes patients, individuals who added other antidiabetic medications during the study period, and participants who refused to be involved were excluded from the study. Results: The study included participants aged between 42 and 85 years, with a mean age of 65.38 years, and the majority (58.7%) were males. There was a significant weight and BMI reduction observed in all patients, with P values <0.001 for both. The average weight reduction was 2.97 kg (SD = 2.34, 95% CI 1.65-3.30), and the average Body (BMI) reduction was 1.16 (SD = 0.91, 95% CI 1.03-1.29). A vast majority of participants (98.5%) reported a weight loss of at least 1 kg, and 13.8% of participants experienced a change in BMI category from higher to lower. No patients reported an increase in the BMI category. There was a significant reduction in glycohemoglobin (HbA1c) measurements from 9.18 pretreatment to 8.13 posttreatment, with an average reduction of 1.05 units (SD = 1.84, 95% CI 0.79-1.31). The majority of participants (70.9%) reported a reduction in HbA1c of at least 0.1 unit. Although there was a slight decrease in estimated glomerular filtration rate (eGFR) values on average (1.35 units), the change was not statistically significant (P = 0.059). More than half of the participants (51.5%) reported an increase in eGFR, 45.4% reported a decrease, and 3.1% reported no change. There was a statistically significant reduction in urinary albumin-to-creatinine ratio (UACR) values from a median of 5.97 pretreatment to a median of 5.60 post-treatment. The median decrease was 0.72 units, with one-third (33.3%) reporting an increase and two-thirds (66.7%) reporting a decrease in values. The correlation analysis revealed no significant association between the total quantity of semaglutide taken and the magnitude of changes. Conclusion: Our study on the impact of weekly semaglutide in adults with T2DM reveals positive effects on kidney outcomes, including weight loss, glycemic control and improved urine albumin creatine ratio, and a reduced risk of nephropathy. These findings highlight the potential of semaglutide as a safe and effective treatment option for improving renal health in individuals with T2DM.

Efficacy of Low-Dose Isotretinoin in the Treatment of Rosacea: A Systematic Review and Meta-Analysis.

Rosacea is a common cutaneous condition caused by persistent, recurring lesions in facial skin vessels. It is a chronic skin condition with a variety of clinical symptoms and an unknown cause. Rosacea begins with the widening of capillaries and a flushed appearance. Following that, telangiectasia appears, and reddened patches persist, particularly on the cheeks and nose. Erythema persists due to repeated vasodilation and telangiectasia. In addition, skin inflammation manifests as papules, pustules, lymphedema, and fibrosis. Despite recent advances in treatment, rosacea, a chronic inflammatory relapsing central facial dermatosis, can be extremely difficult to manage.  The purpose of this meta-analysis and systematic review was to evaluate the effectiveness of low-dose isotretinoin in the treatment of rosacea. Following the guidelines set forth by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA), the researcher employed the following search terms in the EMBASE, Web of Science, PubMed, Cochrane Library, and Google Scholar databases to provide a therapeutic update relevant to clinical practice: "low dose isotretinoin," "isotretinoin and rosacea," "isotretinoin treatment of rosacea," and "effectiveness of isotretinoin in treating rosacea". The search was carried out by the researcher for articles published from February 2019 to February 2024. The articles included were all published in the English language. The overall frequency of patients with adverse events differed significantly between the groups treated with low-dose isotretinoin and the comparators (minocycline, pulsed dye laser, evening primrose oil, Lactobacillus plantarum, doxycycline, combined dose or placebo) (0.80, 95% CI 0.73 to 0.88, p = 0.0001). Sub-group analysis indicated that there was a difference between the interventions used in the treatments all in favor of low-dose isotretinoin treatment. The results showed that the moderate group had RR: 0.76, 95% CI: 0.44-1.30, I2 = 0%; the mild group had RR: 0.94, 95% CI: 0.56-1.57, I2 = 0%; and the group with severe rosacea had RR: 0.73, 95% CI: 0.47-1.13, I2 = 0%. According to this study, rosacea can be treated effectively with low-dose isotretinoin even in patients at severe stages of the disease by using the recommended dose once a week. Further, the intervention has also been shown to have fewer side effects on the patients. Therefore, this study recommends randomized controlled trials to be done to fully investigate the best combination options for isotretinoin on mild to severe rosacea based on the fact that some of the treatments combined have shown to be effective on treatment.

Comparison of Remotely Applied and Face-to-Face Disease Activity Scores in Saudi Arabian Patients With Rheumatoid Arthritis: A Prospective Cohort Study.

OBJECTIVES:  This study aimed to assess the disease activity indices (DAI) of rheumatoid arthritis (RA) by telephone-based tele-visits compared to face-to-face clinic encounters. METHODS: Patients with RA attending outpatient clinics between December 2021 and May 2022 were prospectively recruited. Disease activity assessments were initially performed in the clinic using the disease activity score 28-C-reactive protein (DAS28-CRP) and disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR). Within two weeks of the clinic visit, a telephone-based assessment gathered information on demographics, Routine Assessment of Patient Index Data 3 (RAPID3) score, and satisfaction. Disease activity scores were dichotomized into remission or low disease activity and moderate to high disease activity. RESULTS:  A total of 78 patients completed the two-point interview. Of those, 62 (79.49%) were women, with a mean age of 54.73±13.71 years. Seropositivity for rheumatoid factor and/or anti-citrullinated peptide was observed in 51 (83.61%) participants. Twenty-seven percent of the patients were classified as in remission or low disease activity by RAPID3. This was 71% for DAS28-CRP and 33% for DAS28-ESR. Based on the dichotomized disease activity classification, the agreement percentage between RAPID3 and DAS28-ESR was 78.08%, while it was 47.22% between RAPID3 and DAS28-CRP, which resulted in kappa statistic values of 0.48 (moderate agreement) and 0.14 (low agreement), respectively. Satisfaction rates were low. CONCLUSION:  Telephone-based RAPID3 showed a low-moderate agreeability compared to DAS28 and had low satisfaction rates. This suggests that tele-rheumatology care by this means was not feasible for following up with patients with RA and warrants further development.

Exploring the Relationship Between Burnout, Resilience, and Dropout Intention Among Nursing Students During Clinical Training in Saudi Arabia.

Background: The issue of burnout syndrome among health discipline students is gaining heightened attention due to its serious effects, which causes them to have the intention to quit. Despite this, limited studies are available on the extent of burnout and its association with resilience and intention to drop out among clinical-level nursing students. Objective: To explore the relationship between burnout, resilience, and intention to quit among nursing students. Methods: An online questionnaire was used to conduct a cross-sectional study, targeting nursing students at the clinical level through a nonprobability sample. The participants were required to provide their sociodemographic, Maslach Burnout Inventory, and Connor-Davidson Resilience Scale. Data was analyzed using descriptive, inferential, and correlation tests. Results: The study included a group of 564 nursing students and interns, the majority of whom were female at a percentage of 78.9%. Among this group, 65% experienced a high level of burnout, with 42% experiencing emotional exhaustion, 54% experiencing depersonalization (DP), and 77% reporting low personal achievement. A total of 48% of clinical-level students were considering quitting the nursing program. Moreover, the students reported low scores of resilience, with negative correlations observed with DP (r = -.12, p = .04) and positive correlation with low personal achievement (r = .43, p < .001). Conclusion: Nursing students and interns faced a significant amount of burnout and showed a desire to drop out nursing program. Their level of resilience was moderately low, and it correlated with burnout subscales DP and personal accomplishment. A collaborative intervention is needed to promote resiliency and alleviate burnout symptoms during clinical training.

Integration of immunoinformatics and cheminformatics to design and evaluate a multitope vaccine against Klebsiella pneumoniae and Pseudomonas aeruginosa coinfection.

Introduction: Klebsiella pneumoniae (K. pneumoniae) and Pseudomonas aeruginosa (P. aeruginosa) are the most common Gram-negative bacteria associated with pneumonia and coinfecting the same patient. Despite their high virulence, there is no effective vaccine against them. Methods: In the current study, the screening of several proteins from both pathogens highlighted FepA and OmpK35 for K. pneumonia in addition to HasR and OprF from P. aeruginosa as promising candidates for epitope mapping. Those four proteins were linked to form a multitope vaccine, that was formulated with a suitable adjuvant, and PADRE peptides to finalize the multitope vaccine construct. The final vaccine's physicochemical features, antigenicity, toxicity, allergenicity, and solubility were evaluated for use in humans. Results: The output of the computational analysis revealed that the designed multitope construct has passed these assessments with satisfactory scores where, as the last stage, we performed a molecular docking study between the potential vaccine construct and K. pneumonia associated immune receptors, TLR4 and TLR2, showing affinitive to both targets with preferentiality for the TLR4 receptor protein. Validation of the docking studies has proceeded through molecular dynamics simulation, which estimated a strong binding and supported the nomination of the designed vaccine as a putative solution for K. pneumoniae and P. aeruginosa coinfection. Here, we describe the approach for the design and assessment of our potential vaccine.

Molecular and Biological Investigation of Isolated Marine Fungal Metabolites as Anticancer Agents: A Multi-Target Approach.

Cancer is the leading cause of death globally, with an increasing number of cases being annually reported. Nature-derived metabolites have been widely studied for their potential programmed necrosis, cytotoxicity, and anti-proliferation leading to enrichment for the modern medicine, particularly within the last couple of decades. At a more rapid pace, the concept of multi-target agents has evolved from being an innovative approach into a regular drug development procedure for hampering the multi-fashioned pathophysiology and high-resistance nature of cancer cells. With the advent of the Red Sea Penicillium chrysogenum strain S003-isolated indole-based alkaloids, we thoroughly investigated the molecular aspects for three major metabolites: meleagrin (MEL), roquefortine C (ROC), and isoroquefortine C (ISO) against three cancer-associated biological targets Cdc-25A, PTP-1B, and c-Met kinase. The study presented, for the first time, the detailed molecular insights and near-physiological affinity for these marine indole alkaloids against the assign targets through molecular docking-coupled all-atom dynamic simulation analysis. Findings highlighted the superiority of MEL's binding affinity/stability being quite in concordance with the in vitro anticancer activity profile conducted via sulforhodamine B bioassay on different cancerous cell lines reaching down to low micromolar or even nanomolar potencies. The advent of lengthy structural topologies via the metabolites' extended tetracyclic cores and aromatic imidazole arm permitted multi-pocket accommodation addressing the selectivity concerns. Additionally, the presence decorating polar functionalities on the core hydrophobic tetracyclic ring contributed compound's pharmacodynamic preferentiality. Introducing ionizable functionality with more lipophilic characters was highlighted to improve binding affinities which was also in concordance with the conducted drug-likeness/pharmacokinetic profiling for obtaining a balanced pharmacokinetic/dynamic profile. Our study adds to the knowledge regarding drug development and optimization of marine-isolated indole-based alkaloids for future iterative synthesis and pre-clinical investigations as multi-target anticancer agents.

Leisure screen time predicts free sugar consumption in children.

OBJECTIVE: This study aimed to investigate free sugar consumption (FSC) in relation to leisure screen time in children. METHODS: Cross-sectional data of 424 healthy Saudi children ages 6 to 12 y were included in this study. Data pertaining to sociodemographic characteristics and leisure screen time (including time spent viewing TV, gaming, and use of electronic devices [e.g., computer, tablet, and smartphone]) in children were collected from mothers via an online questionnaire. A phone interview was later conducted with the mother and child to assess FSC using a previously validated 40-item food frequency questionnaire. RESULTS: Our data found that a large proportion of children exceeded the maximum limit of screen time recommended for children, of ≤2 h/d (61.7%; n = 262). Child and maternal ages and child's birth order among siblings were significantly associated with the duration of leisure screen time (screen time within the recommendation of ≤2 h/d versus screen time that exceeded the recommendation; P < 0.050). Exceeding the recommendation of screen time predicted an increase of 8.96 g/d of FSC from liquid foods, 10.7 g/d of FSC from solid foods, and 19.3 g/d of total FSC. CONCLUSIONS: Exceeding the recommendation of screen time is associated with greater FSC in children. Future interventions should be directed toward restricting screen time and FSC in children.

Individual, familial and country-level factors associated with oral hygiene practices in children: an international survey.

BACKGROUND: Maintaining good oral hygiene is key to preventing dental caries and periodontal disease. Children and adolescents with good oral hygiene behaviours are likely to grow into adults with the same behaviours. This study assessed the frequency of using various oral hygiene methods among children and adolescents from different countries and individual, familial and country-level factors associated with the use of these methods. METHODS: A multi-country online survey collected data from caregivers of children in 2020-21 about children's use of oral hygiene methods including toothbrush, fluoridated toothpaste, mouthwash, dental floss and miswak using self-administered, close-ended questions. Adjusted multilevel logistic regression models were used to assess the relationship between each of the five oral hygiene methods (dependent variables) and the independent factors: sex, age, and history of dental visits (individual factors), mother's education and area of residence (familial factors) as well as country income and region (country-level factors). RESULTS: A total of 4766 parents/caregivers were included from 20 countries (77.4% Eastern Mediterranean-region and 41.6% lower middle income countries). The most frequent oral hygiene methods were using toothbrush and toothpaste (90% and 60.3%). The use of oral hygiene methods differed by age, sex and history of dental visits as well as mother's education and area of residence (P < 0.05). In addition, children from low income countries had significantly lower odds of using mouthwashes and dental floss than those from high income countries (AOR = 0.55, 95% CI 0.31, 0.98 and AOR = 0.34, 95% CI 0.12, 0.97) whereas children from the European region had higher odds of using mouthwash (AOR = 2.82, 95% CI 1.27, 6.26) and those from the region of the Americas had higher odds of using dental floss (AOR = 3.84, 95% CI 1.28, 11.52) than those from the Eastern Mediterranean region. CONCLUSIONS: The use of various oral hygiene methods is associated with individual, familial and country-level factors. Oral health promotion programs should be developed taking into account these influences.

Euclea divinorum Hiern: Chemical Profiling of the Leaf Extract and Its Antioxidant Activity In Silico, In Vitro and in Caenorhabditis elegans Model.

Euclea divinorum Hiern is a medicinal plant widely distributed in the northeast parts of South Africa. This plant has been used to treat miscarriage and to alleviate gastrointestinal problems. It can also be used externally for the treatment of ulcers and gonorrhea. In this study, we investigated the phytochemical composition of E. divinorum leaf extract using LC-MS and explored its antioxidant properties in vitro and in vivo. The total polyphenolic content of the extract was determined by the Folin-Ciocalteu method. DPPH and FRAP assays were employed to confirm the plant's antioxidant potential in vitro. A survival assay in the Caenorhabditis elegans model was used to evaluate the extract's ability to counteract juglone-induced oxidative stress. Moreover, a docking study was performed for the extract's metabolites, in order to predict possible molecular targets that could explain the antioxidant effect of the plant on a molecular level. This in silico approach was accomplished on three different proteins; xanthine oxidase enzyme, heat shock protein 90 (Hsp90), and induced nitric oxide synthase (iNOS). Docking scores of the resulting poses and their interactions with binding sites' residues were explored for each protein and were compared to those of simultaneously docked respective co-crystallized and reference substrates. The extract furnished promising antioxidant activities in vitro and in vivo in the C. elegans model that might be attributed to the presence of 46 compounds, which showed several interactions and low binding scores with the tested enzymes. In conclusion, E. divinorum is a promising, safe, and effective antioxidant candidate that could be used to ameliorate oxidative stress-related disorders.

Pediatric Allergic Fungal Rhinosinusitis: Does Age Make a Difference?

Background Allergic fungal rhinosinusitis (AFRS) is a hypersensitive response to fungi within the sinus cavity. Children represent a challenging group of patients with sinonasal disorders, as their sinus anatomy is not fully developed. This study aimed to determine the various clinical manifestations and management outcomes in children with AFRS. Methods A retrospective chart review of children who underwent sinus surgery for AFRS at a tertiary healthcare center between 2005 and 2021 was performed. Demographics, clinical manifestations, radiological and laboratory results, treatment regimens, complications, and recurrence rates were collected. Subanalysis was performed based on age at first surgery: group A (<13 years) and group B (≥13 years). Results Overall, 35 children underwent sinus surgery for AFRS during the study period. The mean patient age at the time of surgery was 14 years. Bilaterality was present in 15/35 (42.9%) patients and anosmia in 12/35 (34.3%). Polyps on examination were present in 31/35 (88.6%) patients and proptosis in 8/35 (22.9%). Sub-analysis revealed that group A showed less bilateral disease (11.4%) than group B (31.4%) and a lower Lund-Mackay score (median=11.50 and 17, respectively, p=0.002). Conclusion Age at surgery did not have an impact on the outcome. A high index of suspicion should be exercised when dealing with children with sinonasal symptoms that do not respond to routine treatment and should be investigated for chronic sinusitis.

Phragmanthera austroarabica A.G.Mill. and J.A.Nyberg Triggers Apoptosis in MDA-MB-231 Cells In Vitro and In Vivo Assays: Simultaneous Determination of Selected Constituents.

Phragmanthera austroarabica (Loranthaceae), a semi-parasitic plant, is well known for its high content of polyphenols that are responsible for its antioxidant and anti-inflammatory activities. Gallic acid, catechin, and methyl gallate are bioactive metabolites of common occurrence in the family of Loranthaceae. Herein, the concentrations of these bioactive metabolites were assessed using high-performance thin layer chromatography (HPTLC). Methyl gallate, catechin, and gallic acid were scanned at 280 nm. Their concentrations were assessed as 14.5, 6.5 and 43.6 mg/g of plant dry extract, respectively. Phragmanthera austroarabica extract as well as the three pure compounds were evaluated regarding the cytotoxic activity. The plant extract exhibited promising cytotoxic activity against MDA-MB-231 breast cells with the IC50 value of 19.8 µg/mL while the tested pure compounds displayed IC50 values in the range of 21.26-29.6 µg/mL. For apoptosis investigation, P. austroarabica induced apoptotic cell death by 111-fold change and necrosis by 9.31-fold change. It also activated the proapoptotic genes markers and inhibited the antiapoptotic gene, validating the apoptosis mechanism. Moreover, in vivo studies revealed a significant reduction in the breast tumor volume and weight in solid Ehrlich carcinoma (SEC) mice. The treatment of SEC mice with P. austroarabica extract improved both hematological and biochemical parameters with amelioration in the liver and kidney histopathology to near normal. Taken together, P. austroarabica extract exhibited promising anti-cancer activity through an apoptosis-induction.

Metabolic Profiling, Chemical Composition, Antioxidant Capacity, and In Vivo Hepato- and Nephroprotective Effects of Sonchus cornutus in Mice Exposed to Cisplatin.

Sonchus cornutus (Asteraceae) is a wild. edible plant that represents a plentiful source of polyphenolic compounds. For the first time, the metabolic analysis profiling demonstrated the presence of anthocyanidin glycosides, coumarins, flavonoids and their corresponding glycosides, and phenolic acids. The total phenolic compounds were determined to be 206.28 ± 14.64 mg gallic acid equivalent/gm, while flavonoids were determined to be 45.56 ± 1.78 mg quercetin equivalent/gm. The crude extract of S. cornutus exhibited a significant 1,1-diphenyl-2-picrylhydrazyl free radical scavenging effect with half-maximal inhibitory concentration (IC50) of 16.10 ± 2.14 µg/mL compared to ascorbic acid as a standard (10.64 ± 0.82 µg/mL). In vitro total antioxidant capacity and ferric reducing power capacity assays revealed a promising reducing potential of S. cornutus extract. Therefore, the possible protective effects of S. cornutus against hepatic and renal toxicity induced by cisplatin in experimental mice were investigated. S. cornutus significantly ameliorated the cisplatin-induced disturbances in liver and kidney functions and oxidative stress, decreased MDA, ROS, and NO levels, and restored CAT and SOD activities. Besides, it reversed cisplatin-driven upregulation in inflammatory markers, including iNOS, IL-6, and IL-1ß levels and NF-κB and TNF-α expression, and elevated anti-inflammatory IL-10 levels and Nrf2 expression. Additionally, the extract mitigated cisplatin alteration in apoptotic (Bax and caspase-3) and anti-apoptotic (Bcl-2) proteins. Interestingly, hepatic, and renal histopathology revealed the protective impacts of S. cornutus against cisplatin-induced pathological changes. Our findings guarantee a protective effect of S. cornutus against cisplatin-induced hepatic and renal damage via modulating oxidative stress, inflammation, and apoptotic pathways.

Meleagrin Isolated from the Red Sea Fungus Penicillium chrysogenum Protects against Bleomycin-Induced Pulmonary Fibrosis in Mice.

The Red Sea marine fungus Penicillium chrysogenum (Family: Ascomycota) comprises a panel of chemically diverse natural metabolites. A meleagrin alkaloid was isolated from deep-sediment-derived P. chrysogenum Strain S003 and has been reported to exert antibacterial and cytotoxic activities. The present study aimed to explore the therapeutic potential of meleagrin on pulmonary fibrosis. Lung fibrosis was induced in mice by a single intratracheal instillation of 2.5 mg/kg bleomycin. Mice were given 5 mg/kg meleagrin daily either for 3 weeks after bleomycin administration in the treatment group or 2 weeks before and 3 weeks after bleomycin administration in the protection group. Bleomycin triggered excessive ROS production, inflammatory infiltration, collagen overproduction and fibrosis. Bleomycin-induced pulmonary fibrosis was attenuated by meleagrin. Meleagrin was noted to restore the oxidant-antioxidant balance, as evidenced by lower MDA contents and higher levels of SOD and catalase activities and GSH content compared to the bleomycin group. Meleagrin also activated the Nrf2/HO-1 antioxidant signaling pathway and inhibited TLR4 and NF-κB gene expression, with a subsequent decreased release of pro-inflammatory cytokines (TNF-α, IL-6 and IFN-γ). Additionally, meleagrin inhibited bleomycin-induced apoptosis by abating the activities of pro-apoptotic proteins Bax and caspase-3 while elevating Bcl2. Furthermore, it suppressed the gene expression of α-SMA, TGF-ß1, Smad-2, type I collagen and MMP-9, with a concomitant decrease in the protein levels of TGF-ß1, α-SMA, phosphorylated Smad-2, MMP-9, elastin and fibronectin. This study revealed that meleagrin's protective effects against bleomycin-induced pulmonary fibrosis are attributed to its antioxidant, anti-inflammatory, anti-apoptotic and antifibrotic properties. Notably, the use of meleagrin as a protective agent against bleomycin-induced lung fibrosis was more efficient than its use as a treatment agent.

Metabolomics-Based Profiling of Clerodendrum speciosum (Lamiaceae) Leaves Using LC/ESI/MS-MS and In Vivo Evaluation of Its Antioxidant Activity Using Caenorhabditis elegans Model.

We investigated the antioxidant activity of the total methanol extract of C. speciosum leaves (CST), the ethyl acetate (CSE), and the remaining aqueous (CSR) fractions in vitro, in vivo using Caenorhabditis elegans model, and in silico. LC-ESI-MS/MS analysis was employed for metabolic profiling of CST. ADME/TOPAKT prediction was performed to determine the potential pharmacokinetic, pharmacodynamic, and toxicity properties of the major identified phytoconstituents. All examined samples showed considerable antioxidant activity where CST, CSE, and CSR displayed EC50 values of 27.1, 16.2, and 21.3 µg/mL, respectively, in 2,2-diphenyl-1-picrylhydrazyl (DPPH•) assay, whereas they showed 11.44, 16.27, and 12.16 Fe2+ equivalents/mg of sample, respectively, in ferric reducing antioxidant power (FRAP) assay. CST, CSE, and CSR displayed total phenolic content of 262, 326, and 289 mg GAE/g sample, respectively. In vivo antioxidant study revealed that CST at 150 µg/mL increased the survival rate of C. elegans by 71.88% compared to untreated group. Regarding intracellular reactive oxygen species (ROS), worms treated with 150 µg/mL of CSE exhibited 60.42% reduction of ROS compared to the untreated group. Quantitation of hsp-16.2/GFP expression in Caenorhabditis elegans showed that worms treated with 150 µg/mL of CSR exerted 40.43% reduction in fluorescence with respect to the untreated group. LC-ESI-MS/MS of CST revealed the presence of sixteen secondary metabolites belonging mainly to polyphenolics with phenyl propanoids constituting the major detected class. The in silico study showed that rosmarinic acid displayed the best fitting within the active sites of Daf-2 protein with considerable safety profile and limited pharmacokinetic and pharmacodynamic that could be slightly enhanced by certain treatment.

FTIR Characterization of Sulfated Polysaccharides Obtained from Macrocystis integrifolia Algae and Verification of Their Antiangiogenic and Immunomodulatory Potency In Vitro and In Vivo.

The aim of this study was to evaluate the antiangiogenic and immunomodulatory potential of sulfated polysaccharides from the marine algae Macrocystis integrifolia characterized by FTIR. The cytotoxicity of sulfated polysaccharides was evaluated using the 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) assay. Antiangiogenic activity was evaluated using the chicken chorioallantoic membrane (CAM) assay. Immunomodulatory activity was determined on macrophage functionality and allergic response. The results showed that sulfated polysaccharides significantly decreased angiogenesis in chicken chorioallantoic membranes (p < 0.05). Likewise, they inhibited in vivo chemotaxis and in vitro phagocytosis, the transcription process of genes that code the enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and nitric oxide synthase-2 (NOS-2) and the nuclear factor kappa-light chain enhancer of activated B cells (NF-κB), showing immunomodulatory properties on the allergic response, as well as an in vivo inhibitory effect in the ovalbumin-induced inflammatory allergy model (OVA) and inhibited lymphocyte proliferation specific to the OVA antigen in immunized mice. Finally, these compounds inhibited the histamine-induced skin reaction in rats, the production of immunoglobulin E (IgE) in mice, and the passive response to skin anaphylaxis in rats. Therefore, the results of this research showed the potential of these compounds to be a promising source for the development of antiangiogenic and immunomodulatory drugs.

Evaluation of The Antioxidant, Antimicrobial, and Anticancer Activities of Dicliptera bupleuroides Isolated Compounds Using In Vitro and In Silico Studies.

Phytochemical investigation of chloroform fraction (DBC) and ethyl acetate fraction (DBE) of D. bupleuroides (Acanthaceae) resulted in the isolation of ß-sitosterol (1) from DBC and vanillic acid (2) from DBE, which were first to be isolated from D. bupleuroides. ß-Sitosterol (1) exhibited substantial antioxidant activity (IC50 = 198.87 µg/mL), whereas vanillic acid (2) showed significant antioxidant power (IC50 = 92.68 µg/mL) employing 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical scavenging capacity assay. Both compounds showed pronounced antimicrobial activity using the agar disc diffusion method, particularly against fungi showing MIC values of 0.182 and 0.02 concerning Candida albicans, respectively, and 0.001 mg/mL regarding Penicillium notatum. They revealed considerable antibacterial activity with MIC values ranging between 0.467 and 0.809 mg/mL. Vanillic acid (2) exhibited substantial anticancer potential displaying 48.67% cell viability at a concentration of 100 µg/mL using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-Diphenyl-2H-Tetrazolium Bromide) assay concerning HepG2 cell lines. These results were further consolidated by in silico studies on different enzymes, where vanillic acid displayed a high fitting score in the active pockets of DNA-gyrase, dihydrofolate reductase, aminoglycoside nucleotidyltransferase, and ß-lactamase. It also inhibited human cyclin-dependent kinase 2 (CDK-2) and DNA topoisomerase II, as revealed by the in silico studies. ADME/TOPKAT (absorption, distribution, metabolism, excretion, and toxicity) prediction showed that vanillic acid exhibited reasonable pharmacodynamic, pharmacokinetic, and toxicity properties and, thus, could perfectly together with D. bupleuroides crude extract be incorporated in pharmaceutical preparations to counteract cancer and microbial invasion, as well as oxidative stress. Thus, it is concluded that D. bupleroides could be a potential source of therapeutically active compounds, which would be helpful for the discovery of clinically effective and safe drugs.

New Multi-Targeted Antiproliferative Agents: Design and Synthesis of IC261-Based Oxindoles as Potential Tubulin, CK1 and EGFR Inhibitors.

A series of 3-benzylideneindolin-2-one compounds was designed and synthesized based on combretastatin A-4 and compound IC261, a dual casein kinase (CK1)/tubulin polymerization inhibitor, taking into consideration the pharmacophore required for EGFR-tyrosine kinase inhibition. The new molecular entities provoked significant growth inhibition against PC-3, MCF-7 and COLO-205 at a 10 µM dose. Compounds 6-chloro-3-(2,4,6-trimethoxybenzylidene) indolin-2-one, 4b, and 5-methoxy-3-(2,4,6-trimethoxybenzylidene)indolin-2-one, 4e, showed potent activity against the colon cancer COLO-205 cell line with an IC50 value of 0.2 and 0.3 µM. A mechanistic study demonstrated 4b's efficacy in inhibiting microtubule assembly (IC50 = 1.66 ± 0.08 µM) with potential binding to the colchicine binding site (docking study). With an IC50 of 1.92 ± 0.09 µg/mL, 4b inhibited CK1 almost as well as IC261. Additionally, 4b and 4e were effective inhibitors of EGFR-TK with IC50s of 0.19 µg/mL and 0.40 µg/mL compared to Gifitinib (IC50 = 0.05 µg/mL). Apoptosis was induced in COLO-205 cells treated with 4b, with apoptotic markers dysregulated. Caspase 3 levels were elevated to more than three-fold, while Cytochrome C levels were doubled. The cell cycle was arrested in the pre-G1 phase with extensive cellular accumulation in the pre-G1 phase, confirming apoptosis induction. Levels of cell cycle regulating proteins BAX and Bcl-2 were also defective. The binding interaction patterns of these compounds at the colchicine binding site of tubulin and the Gifitinib binding site of EGFR were verified by molecular docking, which adequately matched the reported experimental result. Hence, 4b and 4e are considered promising potent multitarget agents against colon cancer that require optimization.