Introduction: Sinomenine, derived from Sinomenium acutum, has been reported as a potential treatment for morphine addiction but its mechanisms are poorly understood. Hence this study was conducted to investigate the potential mechanisms underlying sinomenine effects on morphine addiction. Materials and methods: Potential protein targets for sinomenine were predicted using SwissTarget Prediction and PharmMapper while morphine addiction targets were collected from DisGeNet and GeneCards databases. Protein-protein interaction was examined using GeneMANIA web server while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted using ShinyGO online tool. Topological network analysis was performed using Cytoscape to measure the degree centrality, betweenness centrality and closeness centrality values while molecular docking analysis was done using AutoDock Vina to determine the binding energies and interactions. Results: A total of 15 sinomenine targets were identified to be involved. Among the identified targets, 37.94% shared protein domains and 19.64% displayed physical interactions. Relevant biological processes, molecular functions, cellular components and signalling pathways were identified involving G-protein coupled opioid receptor signalling pathways and activities, integral component of presynaptic membrane and mitophagy. Molecular docking suggested that the substituted aromatic ring of sinomenine plays important roles in the binding to the protein targets. The top five most significant protein targets were identified based on the binding energies and degree centrality values, namely OPRD1, OPRK1, NOS1, OPRM1 and SRC. Conclusion: Sinomenine interacted with various protein targets and pathways which can potentially treat morphine addiction mainly via opioid receptors and their signalling pathways

OBJECTIVE: To explore the potential apoptotic mechanisms of 3 Morchella extracts (Morchella conica, Morchella esculenta and Morchella delicosa) on breast and colon cancer cell lines using apoptotic biomarkers. METHODS: Human breast cell line (MCF-7) and colon cancer cell line (SW-480) were treated with methanol and ethanol extracts of 3 Morchella species with concentration ranging from 0.0625 to 2 mg/mL. After that their effects on gene expression of apoptosis related markers (pro-apoptotic markers including Bax, caspase-3, caspase-7, and caspase-9, and the antiapoptotic marker including Bcl-2) were determined using reverse transcription polymerase chain reaction. RESULTS: All Morchella extracts reduced breast and colon cancer cells proliferation at half inhibitory concentration (IC₅₀) of 0.02 ±0.01 to 0.68 ±0.30 mg/mL. As expected, all Morchella extracts significantly increased gene expressions of Bax, caspase-3, caspase-7, and caspase-9 and downregulated the gene expression of Bcl-2 in MCF-7 and SW-480 cell lines (P<0.05). CONCLUSIONS Morchella extracts demonstrated significant anti-proliferative activity against breast and colon cancer cell lines via an apoptosis induction mechanism. Anticancer activity of Morchella extracts and activation of apoptosis in breast and colon cancer cells suggest that it may be used to develop chemotherapeutic agents against cancer in future.
Humans ; Apoptosis/genetics* ; Colonic Neoplasms/drug therapy* ; Breast Neoplasms/drug therapy* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Plant Extracts/pharmacology* ; Gene Expression Regulation, Neoplastic/drug effects* ; MCF-7 Cells ; Ascomycota/chemistry*

Thymoquinone (Tq) and gallic acid (GA) are known for counter-tumorigenic characteristics. GA inhibits cancer cell proliferation by interfering with many apoptotic signaling pathways, producing more reactive oxygen species (ROS), focusing on the cell cycle, and suppressing the expression of oncogenes and matrix metalloproteinases (MMPs). In this study, thymoquinone (after reducing to thymohydroquinone) and gallic acid are esterified to form thymohydroquinyl gallate (a prodrug). Thymohydroquinyl gallate (THQG) possesses enhanced antineoplastic efficacy and targeted delivery potential. The chemical and spectroscopic analysis confirms ester synthesis. Gold nanoparticles (AuNPs) are employed as nanocarriers due to their physicochemical and optical characteristics, biocompatibility, and low toxicity. As an efficient drug transporter, gold nanoparticles (AuNPs) shield conjugated drugs from enzymatic digestion. The prodrug acts as a reducing agent for Au metal atoms and is loaded onto it after reduction. The nano drug is radiolabeled with ^99mTc and ¹³¹I to monitor the drug biodistribution in animals using a gamma camera and single-photon emission computerized tomography (SPECT). ¹³¹I is an antineoplastic that helps enhance the drug's efficiency. Chromatographic results reveal promising radiolabeling percentages. In vitro, drug release shows sustained release at pH⁓5.8. In vitro 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) cytotoxicity assay reveals drug potency on CAL 27 and MCF 7 cell lines.

Purpose: This study was performed to investigate the pattern of condylar pressure distribution in the discs of a patient diagnosed with disc displacement without reduction. Materials and Methods: This research consisted of a pre- and post-test observational clinical study. A patient diagnosed with disc displacement without reduction underwent treatment with an occlusal splint for 3 months. Finite element analysis employed a 3-dimensional model constructed from magnetic resonance images of the patient, taken both before the application of the splint and 3 months after its use. Results: The post-test model demonstrated a decrease in condylar pressure on the disc, with measurements dropping to 72 MPa from the pre-test level of 143 MPa. In the pre-test, the pressure distribution pattern was concentrated on the lateral posterior border, whereas in the post-test, it shifted toward the intermediate zone of the disc. Conclusion Utilization of a stabilization splint for 3 months resulted in decreased pressure and a marked change in the pressure distribution pattern on the temporomandibular disc.

Objectives: Postmenopausal females often experience genitourinary symptoms like vulvovaginal dryness due to estrogen decline.Hormone replacement therapy is effective in alleviating vaginal atrophy and genitourinary syndrome in this population. Evaluate local estrogen’s safety and effectiveness for alleviating postmenopausal vaginal symptoms, including endometrial thickness, dyspareunia, vaginal pH, and dryness. Methods: We searched Google Scholar, Cochrane Library, ClinicalTrial.Gov, PubMed, and ScienceDirect databases until July 2023. All randomized controlled trials (RCTs) linking intravaginal estrogen supplementation to vaginal atrophy or vaginitis were included. The risk of bias was evaluated with RoB 2, and publication bias was assessed using Egger and Beggs analysis. Results: All evidence pertains to females. Eighteen studies (n = 4,723) compared estrogen with placebo. Patients using estrogen showed a significant increase in superficial cells (mean differences [MD]: 19.28; 95% confidence intervals [CI]: 13.40 to 25.16; I2 = 90%; P < 0.00001) and a decrease in parabasal cells (MD: –24.85; 95% CI: –32.96 to –16.73; I2 = 92%; P < 0.00001). Vaginal pH and dyspareunia significantly reduced in estrogen users (MD: –0.94; 95% CI: –1.05 to –0.84; I2 = 96%) and (MD: –0.52; 95% CI: –0.63 to –0.41; I2 = 99%), respectively. Estrogen did not significantly affect vaginal dryness (MD: –0.04; 95% CI: –0.18 to 0.11; I2 = 88%). Adverse events like vulvovaginal pruritis, mycotic infection, and urinary tract infection were reported, but the association was insignificant (risk ratio: 0.95; 95% CI: 0.88 to 1.02; I2 = 0%). Conclusions Our meta-analysis of 18 RCTs suggests promising potential for intravaginal estrogen therapy in alleviating vaginal atrophy and vaginitis in postmenopausal females.

Objective: The study examined the efficacy of various generations of cephalosporins against biofilms developed by pathogenic S. aureus and E. coli. Methods: The development of biofilms by both bacteria was assessed using petri-plate and microplate methods. Biofilm hydrolysis and inhibition were tested using first to fourth generations of cephalosporins, and the effects were analyzed by crystal violet staining and phase contrast microscopy. Results: Both bacterial strains exhibited well-developed biofilms in petri-plate and microplate assays. Cefradine (first generation) showed 76.78% hydrolysis of S. aureus biofilm, while significant hydrolysis (59.86%) of E. coli biofilm was observed by cefipime (fourth generation). Similarly, cefuroxime, cefadroxil, cefepime, and cefradine caused 78.8%, 71.63%, 70.63%, and 70.51% inhibition of the S. aureus biofilms, respectively. In the case of E. coli, maximum biofilm inhibition (66.47%) was again shown by cefepime. All generations of cephalosporins were more effective against S. aureus than E. coli, which was confirmed by phase contrast microscopy. Conclusions and Relevance: Cephalosporins exhibit dual capabilities of hydrolyzing and inhibiting S. aureus and E. coli biofilms. First-generation cephalosporins exhibited the highest inhibitory activity against S. aureus, while the third and fourth generations significantly inhibited E. coli biofilms. This study highlights the importance of tailored antibiotic strategies based on the biofilm characteristics of specific bacterial strains.

The technetium-99m methylene diphosphonate (99mTc-MDP) whole-body bone scan along with single-photon emission computed tomography (SPECT/CT) can detect challenging soft tissue uptake patterns. We present a case of a 67-year-old female in whom the 99mTc-MDP scan, performed 3 hours after injection, revealed abnormal soft tissue uptake in the right thoracic region. No functioning right kidney was seen in the right lumbar region. Hybrid SPECT/CT revealed an ectopic right kidney in the subdiaphragmatic location, accompanied by gut loops and eventration of the right-sided diaphragm. This case underscores the value of SPECT/CT in identifying and characterizing unexpected anatomical abnormalities, such as ectopic kidneys.

Background: A written asthma action plan (WAAP) is one of the treatment strategies to achieve good asthma control in children. Methods: This randomized controlled trial was conducted to observe the effect of WAAP on asthma control and quality of life using the Asthma Control Questionnaire and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) at baseline and after 3 months. A repeated measure analysis of variance was used to analyze the mean score difference between the two groups. Results: There was no significant difference in mean score for asthma control at baseline between groups (F[degree of freedom (df)]=1.17 [1, 119], P=0.282). However, at 3 months, a significant difference in mean scores between groups was observed (F[df]=7.32 [1, 119], P=0.008). The mean±standard deviation (SD) scores in the intervention and control groups were 0.96±0.53 and 1.21±0.49, respectively. For the analysis of the PAQLQ, no significant difference was observed in the mean score for the quality of life baseline in both groups. There were significant mean score changes for the quality of life (F[df]=10.9 [1, 119], P=0.001) at 3 months follow-up, where those in the intervention group scored a mean±SD score of 6.19±0.45, and those in the control group scored 5.94±0.38. A time-group interaction analysis using repeated-measures analysis of variance showed significant differences in mean score changes (F[df]=5.03 [1, 116], P=0.027) and (F[df]=11.55 [1, 116], P=0.001) where a lower mean score was observed in the intervention group, indicating better asthma control and quality of life, respectively. A significant (P<0.001) negative Pearson correlation between asthma control and quality of life (-0.65) indicated a moderate correlation. Conclusion WAAP, along with standard asthma treatment, improves asthma care.

COVID-19 virus is a causative agent of viral pandemic in human beings which specifically targets respiratory system of humans and causes viral pneumonia. This unusual viral pneumonia is rapidly spreading to all parts of the world, currently affecting about 105 million people with 2.3 million deaths. Current review described history, genomic characteristics, replication, and pathogenesis of COVID-19 with special emphasis on Nigella sativum (N. sativum) as a treatment option. N. sativum seeds are historically and religiously used over the centuries, both for prevention and treatment of different diseases. This review summarizes the potential role of N. sativum seeds against COVID-19 infection at levels of in silico, cell lines and animal models.
Animals ; COVID-19 ; Humans ; Nigella ; Pandemics ; Pathology, Molecular ; SARS-CoV-2

Methods: Fifty-one discs were obtained from patients undergoing surgery for herniated disc. Their ages ranged from 19-65 years, and 31/51 were male. Pre-surgical T1 and T2 weighted lumbar-spine MRIs were analyzed to observe Pfirrmann grade, VEP defects, herniation type, Modic changes, and high-intensity zones (HIZ) at the affected level. Five-micron thick sections were stained with hematoxylin and eosin, Alcian blue periodic acid–Schiff stain; examined for histological degeneration scores (HDS; 0–15), inflammation (0 [absence]–3 [severe]), and presence of cartilaginous endplate (CEP). Three-micron thick sections were stained with protein-gene-product 9.5 and expression was counted/mm2. Data was analyzed, and p<0.05 was considered to indicate statistical significance. Results: VEP defects, Modic changes, and HIZ were respectively observed in 30/51, 16/51, and 6/51 of the samples. CEP was observed in 26/51 samples and in 23/51 with endplate defects. Discs with adjacent VEP defects showed increased HDS (p<0.001) and inflammation (p<0.001). Discs with adjacent Modic changes also revealed increased HDS (p=0.01). Histological sections with CEP showed increased HDS (p<0.001) and inflammation (p<0.001), and nerve density was significantly positively correlated with HDS (r=0.27, p=0.02). Conclusions VEP changes can modulate degeneration and inflammation of herniated discs. Presence of these changes is highly predictive of the occurrence of CEP in herniated discs, which leads to slow resorption and persistent clinical symptoms.