Background: Cranberry (Vaccinium macrocarpon) is a small, red fruit that has been widely recognized for its potential health benefits. The cranberry is rich in antioxidant-rich bioactive chemicals and nutritious components like essential vitamins, minerals, and antioxidants; for example, vitamin C, vitamin E, magnesium, copper, potassium, anthocyanins, flavonoids, phenolic acid, etc. Cranberries are thought to offer a variety of health advantages because they are high in Polyphenols (PPs), which have significant antioxidant activity.
Objectives: The objective of the current study was to evaluate the neuroprotective effect of cranberries on behavioural and neurochemical abnormalities induced by Quinolinic Acid (QA) treatment through Intracerebroventricular (ICV) injection in Wistar rats, as well as to identify the synaptic plasticity and cognition by modulating signaling cascades, such as the ERK and PI3K/AKT pathways, which offer an adjunct treatment to slow or enhance the effects of conventional treatment.
Material and methods: A total of thirty Wistar rats were randomly assigned to several experimental groups. QA (240 nM in normal saline) was administered via ICV. Thereafter, cranberry (0.5g/kg p.o.) with QA, and high-dose cranberry group (2g/kg p.o.) with QA were administered to the animals for 21 days. The dosage of QA and cranberries was chosen based on earlier experimental research.
Result: The study found that cranberries significantly decrease cognitive deficits and motor impairments caused by Quinolinic Acid (QA) in rats. QA treatment affected cognitive function, as demonstrated by the Novel object recognition and the Morris water maze tests, and caused substantial disturbances in motor activity, as demonstrated by rotarod and footprint analyses. QA-treated rats also exhibited higher oxidative and nitrosative stress, lower Glutathione (GSH) levels, higher nitrite and lipid peroxidation, cholinergic dysfunction, and abnormalities in mitochondrial complexes I, II, and IV in the striatum and hippocampus regions. Cranberry (2 g/kg p.o.) significantly enhanced memory, learning, and motor coordination. Cranberry supplementation enhanced GSH levels, decreased MDA concentration, and improved mitochondrial function and cholinergic activity. According to a histological study, cranberries can protect against neuronal degeneration and inflammation.
Conclusion: These findings indicate that cranberries may have neuroprotective properties, presumably through antioxidant, anti-inflammatory, and anti-excitotoxic processes that promote brain plasticity, neurogenesis, and neurotransmitter systems. This establishes the potential of cranberries as a prospective natural treatment for cognitive deficits and neurodegenerative illnesses, suggesting the need for additional research to understand the underlying mechanisms and human application better.
Objective: The objective of this study is to evaluate the role of mycoplasma resistance genes in pediatric mycoplasma pneumonia and to identify the factors that necessitate antibiotic adjustments.
Methods: We retrospectively analyzed clinical data from children diagnosed with mycoplasma pneumonia at Chongqing Medical University Children's Hospital (January-October 2023). We categorized patients based on antibiotic treatment adjustments: the antibiotic adjustment group and the no adjustment group. We compared demographic characteristics, clinical outcomes, and the gene resistance rate that point mutations A2063G and A2064G in the 23S rRNA between groups. Logistic regression was employed to determine the factors prompting a switch from macrolides to alternative antibiotics.
Results: The study included 551 cases, with 341 in the no adjustment group and 210 in the antibiotic adjustment group (54 switched to doxycycline, 156 to levofloxacin). There was no significant difference in the prevalence of resistance genes between the groups (71.8% vs. 71.4%; P=0.916). Significant differences were observed in hospital stay duration, C-reactive protein (CRP), D-dimer, fibrinogen, procalcitonin levels, and lung consolidation (P<0.05). Logistic regression identified elevated CRP and procalcitonin levels as independent predictors of the need for alternative antibiotics.
Conclusion: Resistance genes do not predict the need for second-line antibiotics in pediatric mycoplasma pneumonia; however, elevated CRP, and procalcitonin levels significantly correlate with this necessity.
Background: SRY-Box Transcription Factor 4 (Sox4) has been found to be overexpressed in a number of malignancies and is linked to medication resistance. The underlying mechanism of Sox4 in cisplatin-resistant melanomas, however, remains unknown.
Methods: Immunohistochemistry (IHC) was used to examine the expression of Sox4 in melanoma, pigmented nevi, and normal skin tissue. Induction in vitro was used to create the cisplatin- resistant cell lines SK-MEL-28R and A375R. The CCK8 test was used to determine the IC50 values of cisplatin-resistant cells. Lentivirus shut down Sox4 in SK-MEL-28R and A375R cells. The Affymetrix GeneChip array was then utilized to detect changes in signaling pathways in SK-MEL-28R interfering with Sox4. Western blot, qRT-PCR, flow cytometry, and a caspase 3 activity kit were used to confirm the biological process of Sox4 impacting cisplatin resistance in melanoma.
Results: Sox4 expression in melanoma was substantially higher than in pigmented nevus and normal skin tissue (p<0.05, p<0.01).SK-MEL-28R and A375R melanoma cisplatin-resistant strains were created effectively. They were 12.6 and 10.2 times more resistant to cisplatin, respectively than the parental cells. P-gp protein expression was substantially higher in cisplatinresistant strains than in parental strains. Sox4 inhibition lowered the IC50 value of cisplatin in resistant cells. (The IC50 value of SK-MEL-28R+NC was 122.7 mg/L and 24.4 mg/L for SKMEL- 28R+sh-sox4; the IC50 value of A375R+NC was 40.55 mg/L and 5.99 mg/L for A375R+sh-sox4). Meanwhile, Sox4 knockdown causes S phase arrest and enhanced caspase-3 activity in cisplatin-resistant melanoma cells. Sox4 knockdown led to activation of the P38 signaling pathway in resistant cells, according to genome-wide expression analysis, qRT-PCR, and Western blot detection.
Conclusion: Our findings imply that inhibiting Sox4 can improve the sensitivity of drugresistant melanoma cells to cisplatin via the P38 signaling pathway, thus opening up a new route for melanoma treatment.
Background: Late-Onset Hypogonadism (LOH) is a prevalent age-related condition in men, characterized by a decline in testosterone (T) and associated symptoms.
Objective: This study explored the mechanism of T deficiency in LOH.
Methods: Male SD rats were raised until 20 months of age in order to establish the LOH models. The hormone level and sperm quality were examined. The behavior experiments were carried out to assess whether LOH rats had anxiety and cognitive dysfunction. RNA-seq was used to explore the differential gene in the testis of LOH rats, revealing the molecular mechanism of LOH.
Results: LOH rats exhibited cognitive impairment and anxiety. The sperm quality was decreased, and dysfunction of the Hypothalamic-Pituitary-Gonadal (HPG) axis was observed in LOH rats. Testosterone biosynthesis enzymes (including StAR, Cyp17A1, and HSD17β) were suppressed, reducing T levels. RNA-seq revealed that cholesterol metabolism and steroid hormone biosynthesis were abnormal. The expression of Sterol O-Acyltransferase 2 (SOAT2) was upregulated in the Leydig cells in the testes of LOH rats. Meanwhile, the testicular Cholesterol Ester (CE) increased, and Free Cholesterol (FC) decreased in the LOH rats.
Conclusion: These results indicated that upregulation of SOAT2 decreased FC and increased CE, which led to testosterone deficiency and further affected spermatogenesis and the HPG axis.
Background: The mechanisms of chemotherapy sensitivity and toxicity are complex. Metabolomics can better reflect the status of anticancer drugs, tumors, and hosts simultaneously.
Aim: To identify metabolites and metabolic pathways linked to varying sensitivity and toxicity to chemotherapy in gastric cancer.
Methods: Mice were implanted with human gastric cancer cells through subcutaneous xenografting, and then treated with the PF (platinum-fluorouracil) regimen, with saline serving as the control. Tumor growth was monitored by measuring tumor volume, and body weight was recorded on Days 0, 2, 4, 6, and 8. Kidney damage was assessed using H&E staining. To analyze differential responses, PF-treated mice were grouped separately according to chemotherapy sensitivity (high/medium/low via tumor response) and toxicity (high/medium/low via body weight changes). Serum metabolomics was evaluated using Mass Spectrometry.
Results: Platinum-Fluorouracil (PF) chemotherapy significantly reduced tumor weight in mice (164.7 ± 73.5 mg vs. 334.0 ± 107.5 mg; 54.4% inhibition rate), although it also induced notable body weight loss and renal toxicity compared to controls. Serum metabolomic analysis revealed significant differences between PF and control groups, involving metabolites like deoxymethacin and dehydrocorticosterone, associated with AMPK and cortisol synthesis/secretion pathways. Further comparisons highlighted: (1) High- vs. low-sensitivity subgroups differed significantly in metabolites, such as palmitoyl-CoA and indoleacetic acid (linked to AGE-RAGE, insulin resistance, and AMPK pathways). (2) High- vs. low-toxicity subgroups displayed significant metabolic differences, including methylguanosine and methylcytidine (implicated in ferroptosis, ether lipid, and fatty acid metabolism pathways).
Conclusion: The PF regimen effectively inhibits the growth of subcutaneous tumors in nude mice, while causing varying levels of sensitivity and toxicity in tumor chemotherapy. These observed effects of sensitivity and toxicity are linked to underlying metabolic mechanisms.
Background: Cancer is a major public health concern, and conventional treatments like surgery, chemotherapy, and radiotherapy are associated with several disadvantages, including chemoresistance, toxicity, and economic burden to the family of cancer patients. Thus, discovery of novel agents of natural agents to reduce these side effects is crucial. A series of studies have shown anthraquinones as a promising adjuvant in enhancing the effectiveness of standard cancer therapies.
Objective: This review explores the anticancer potential of anthraquinones and their role in enhancing standard chemotherapy.
Methodology: Various freely available databases, including PubMed, Scopus, Google Scholar and Web of Science were searched for updated and relevant information on anthraquinones and their use as an adjuvant with standard chemotherapeutic agents.
Results: In this article, we looked at the recent developments in the utilization of anthraquinones as adjuvants in chemotherapy. Further, we have elaborated the mechanism of action that anthraquinones target to chemosensitize the drug-resistant cancer cells.
Conclusion: This review provides updated information on emerging role and their potential to be utilized as adjuvants in augmenting the efficacy of conventional cancer therapies.
Background: Observational studies have shown a link between constipation (CN) and psychiatric disorders, including Schizophrenia (SP), Bipolar disorder (BD), Schizoaffective disorder (SD), and Parkinson's disease (PD). However, it is still unknown whether CN affects the occurrence and development of psychiatric disorders or whether psychiatric disorders cause the occurrence and development of CN. Therefore, this study used Mendelian randomization (MR) analysis to evaluate the relationship between CN and psychiatric disorders.
Method: We used genome-wide association studies (GWAS) to assess the relationship between constipation (N = 411, 623) and four psychiatric disorders, including SP ( N = 77, 096), BD (N = 51, 710), SD ( N = 210, 962), PD (N = 482, 730 ), using bidirectional MR analysis. Inverse variance weighting (IVW), MR Egger (ME) and Weighted median (WM) were used as causal analysis methods. Cochran's Q test, funnel plot, MR Egger intercept test and Leave-one-out analysis were used to detect sensitivity. Confounding factors were analyzed and eliminated by LDtrait to avoid influencing the final MR Analysis result.
Results: The results of positive MR analysis indicated that there was no evidence of influence of constipation on SP ( OR 1.043, 95%CI 0.946 - 1.149, P value = 0.398), BD (OR 1.114, 95%CI 0.995 - 1.248, P value = 0.062), SD (OR 0.934, 95%CI 0.674 - 1.294, P value = 0.682) and PD (OR 1.118, 95%CI 0.918 - 1.361, P value = 0.269) under gene prediction. Reverse MR analysis suggested that SP (OR 1.030, 95% CI 1.001-1.060, P value = 0.042) had a causal relationship with constipation. BD (OR 0.993, 95% CI 0.962-1.025, P value = 0.664), SD (OR 1.021, 95% CI 0.984-1.059, P value = 0.265) and PD (OR 1.004, 95% CI 0.974-1.035, P value = 0.790) were not associated with CN.
Conclusion: There was a positive association between SP and CN. CN may have no exact causal relationship with BD, SD and PD, and the interaction mechanism between these diseases needs to be further explored.
Background: Pulsatillae radix (PR), a medicinal root plant and a well-known Chinese herbal remedy, is primarily used for its heat-clearing, detoxifying, blood-cooling, and antiinflammatory properties. This study aimed to investigate the underlying mechanisms by which PR exerts therapeutic effects on ulcerative colitis (UC) through an integrated approach, combining ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS), network pharmacology, and molecular docking.
Methods: The constituents of PR were systematically analyzed using UHPLC-Q-TOF-MS/MS. Potential targets of active components were identified via the SwissTargetPrediction and PharmMapper databases, while UC-related disease targets were retrieved from GeneCard, OMIM, and other relevant databases. Overlapping targets between PR and UC were determined using Venn analysis. Cytoscape software facilitated the construction of the compound-disease-target network. The STRING database was employed to generate a protein-protein interaction (PPI) network for the intersecting targets, and core targets were identified using the CytoNCA plugin. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the DAVID platform. Lastly, molecular docking of key components with target proteins was carried out using PyMOL.
Results: A total of 27 active compounds, 237 drug targets, and 4622 disease targets were identified. Intersection analysis revealed 141 shared targets, while the PPI network identified 10 hub targets. GO and KEGG enrichment analyses indicated that the hub targets were primarily associated with phosphorylation, cytoplasmic functions, nuclear receptor activity, as well as pathways related to the advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling, T cell receptor (TCR) signaling, lipid and cholesterol metabolism, and various cancer-related pathways. Molecular docking experiments demonstrated that (+)- pinoresinol, cichoric acid, β-ecdysone, pulsatilla saponin D, 23-HBA, and AB4 exhibited stable binding to PIK3R1, TLR4, and ESR1, with AB4 forming the most stable complex with ESR1.
Conclusion: This study established a rapid and effective UHPLC-Q-TOF-MS/MS method for characterizing the main chemical components of PR. Using network pharmacology and molecular docking, the active components and potential mechanisms of PR involved in the UC treatment were investigated, providing a foundation for future experimental studies on pharmacodynamics and the underlying mechanisms.
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