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.

Objective:To investigate the effect of Shenfu injection on serum pepsinogen (PG) Ⅰ, PG Ⅱ and gastrin 17 (G17) in sepsis patients with acute gastrointestinal injury (AGI).Methods:From June 2021 to December 2022, a single-center randomized controlled clinical study was conducted to select patients with sepsis complicated with acute gastrointestinal injury (AGI) admitted to the ICU of the Affiliated Hospital of Xuzhou Medical University. Patients were randomly (random number) divided into Shenfu group and control group. All patients were given routine treatment of sepsis according to the guidelines, including treatment of primary disease, fluid resuscitation and supportive management. The Shenfu group was treated with Shenfu injection at the same time as routine treatment. The gastrointestinal injury indicators (PGⅠ, PGⅡ, G17 and AGI grades) before treatment and on the 3rd and 7th days of treatment, and duration of mechanical ventilation and length of ICU stay of the two groups were recorded and compared.Results:A total of 89 sepsis patients with AGI were enrolled, including 44 patients in the Shenfu group and 45 patients in the control group. Before treatment, there was no statistically significant difference in serum PGⅠ, PGⅡ, and G17 between the two groups of patients (all P>0.05). On the 3rd day of treatment, the serum PGⅠ levels in the Shenfu group were significantly lower than the control group [(156.46±62.90) μg/L vs. (183.03±45.44) μg/L, P<0.05]. There was no statistically significant difference in serum PGⅡ and G17 levels between the two groups (both P>0.05). On the 7th day of treatment, the serum levels of PG I, PG II, and G17 in the Shenfu group were significantly lower than those in the control group [(107.97±23.18) μg/L vs. (154.78±33.11) μg/L, (10.73±5.62) μg/L vs. (13.83±6.30) μg/L, (7.31±3.20) pmol/L vs. (9.29±3.92) pmol/L, all P<0.05]. The AGI grading, duration of mechanical ventilation, and length of ICU stay in Shenfu group were significantly reduced than those in the control group (all P<0.05). Conclusion:Shenfu injection can improve the serum gastric function, lower AGI grading, reduce mechanical ventilation time, and the length of ICU stay in sepsis patients with AGI.

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: Cardiovascular disease is a significant contributor to the disease burden in geriatric patients. Underlying systemic inflammation is thought to be the cause of age-related changes in the bone marrow and a major risk factor for atherosclerosis. The purpose of the study was to assess the accuracy of these hematological biomarkers in predicting 30-day mortality in older patients with acute coronary syndrome (ACS). METHODS: This was a prospective observational study of 601 older adult patients (age > 60 years) with ACS who underwent percutaneous coronary intervention over two years (2017-2019). The relationship between baseline hematological parameters and mortality was assessed during the 30-day follow-up. Logistic regression analysis and receiver operating characteristic curve analysis were done to evaluate for diagnostic accuracy of various hematological parameters. RESULTS: The mean age of presentation was 77 ± 17 years. The mean neutrophil-lymphocyte ratio (NLR) value was 5.07 ± 4.90 and the mean platelet-lymphocyte ratio (PLR) value was 108.65 ± 85.82. On univariate analysis, total leucocyte count [odds ratio (OR) = 0.85, P = 0.021], hematocrit (OR = 0.91, P = 0.018), NLR (OR = 1.10, P = 0.001) and PLR (OR = 1.05, P = 0.001) were associated with mortality. On receiver operating characteristic curve analysis, NLR predicted mortality with 68.1% and PLR with 65.7% accuracy. On multivariate analysis, NLR (OR = 1.096, 95% CI: 1.006-1.15, P = 0.035) was an independent predictor of 30-day mortality. CONCLUSIONS For the risk classification of all elderly ACS patients, we highly advise using NLR rather than the total white blood cell count.