Advances in Clinical and Experimental Medicine最新文献

Background: Gecko has been widely documented in Chinese scientific literature as an anti-tumor agent for various illnesses for thousands of years, and more recently, it has been examined for its anti-tumor effects on several cancers. The effect of Gecko microRNAs (miRNAs) on hepatocellular carcinoma (HCC) has not yet been reported.

Objectives: This study was designed to identify miRNAs in Gecko through small RNA sequencing and utilize bioinformatics techniques to construct a potential regulatory network and explore the possible mechanisms of exogenous miRNAs involved in HCC.

Material and methods: RNA was extracted from Gecko tablets, and we screened the Gecko miRNA expression dataset after high-throughput sequencing. Bioinformatics analysis was used to identify novel Gecko and HCC survival-related miRNA-mRNA cross-species regulation networks.

Results: miR-100-5p, miR-99a-5p and miR-101-3p were identified as critical for the role of Geckos in HCC. Nine downstream mRNAs (EZH2, KPNA2, LMNB1, LRRC1, MRGBP, SMARCD1, STMN1, SUB1, and UBE2A) were identified as target genes for critical miRNAs. A miRNA-mRNA regulatory network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed these key mRNAs might be associated with both the suppression and progression of HCC. The novel network significantly correlated with the abundance of multiple immune cells, as determined with immune infiltration analysis.

Conclusions: These findings suggest that Gecko may inhibit progression and exert a therapeutic effect on HCC by targeting critical miRNA-mRNA networks for cross-species regulation. It also provides a reference for future research and development of traditional Chinese medicine (TCM).

Background: Oxidative damage plays an important role in the progression of rheumatoid arthritis (RA). Emerging research evidence suggests that natural antioxidants may effectively ameliorate this disease.

Objectives: To investigate the therapeutic effect of echinacoside (ECH) in a collagen-induced arthritis (CIA) mouse model and thus elucidate the underlying molecular mechanism in RA.

Material and methods: Collagen-induced arthritis mice were intraperitoneally administered 1% dimethyl sulfoxide (DMSO) (control) or 0.6 mg of ECH every other day for 1 month. Arthritis scores and the number of affected paws were assessed. On day 60, mice were euthanized, synovial tissue specimens were obtained, and serum interleukin (IL)-6 and IL-1â expression levels were measured. Mitochondrial morphologies, reactive oxygen species (ROS) content, expression of dynamin-related protein 1 (Drp1), IL-6, nod-like receptor protein 3 (NLRP3), kelch-like ECH-associated protein 1 (Keap1), and nuclear factor-erythroid-2-related factor 2 (Nrf2) contents in synovium were analyzed and compared between DMSOand ECH-treated CIA mice.

Results: Following ECH treatment, mitochondria of CIA-induced mice were found to be elongated, while their arthritis scores, inflammation and the number of affected paws, and the expression levels of Drp1, NLRP3, IL-6, ROS, and Keap1 were all found to be significantly reduced. Conversely, the level of antioxidant factor Nrf2 was found to be elevated. Further, mitochondrial fission was found to be inhibited in synovial tissues.

Conclusions: Our findings validate the therapeutic efficacy of ECH in the CIA mouse model. Echinacoside may suppress oxidative stress and inhibit inflammation by regulating the Nrf2/Drp1 pathway, thus supporting its utility in the treatment of RA.

Psychotic-like experiences (PLEs) refer to sub-threshold hallucinations and delusions observed in both clinical samples and the general population. Psychotic-like experiences have far-reaching implications for an individual's coping strategies and daily functioning. They are associated with both psychotic and non-psychotic disorders. This article presents a comprehensive review of the current literature on PLEs, incorporating a detailed exploration of the definition, prevalence, risk factors, functional impairments, and comorbid psychiatric disorders. Medline/PubMed and Embase were searched to establish and identify the literature. A total of 108 studies met our inclusion criteria. The genetic and biochemical backgrounds of PLEs are discussed, focusing on gene polymorphisms, changes in brain gyrification and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Psychological factors, such as trauma exposure, emotion regulation difficulties, cognitive biases, and attachment issues, were thoroughly examined, especially in terms of their impact on the emergence of PLEs. Here, we show how important the clinical aspects of developmental PLEs are, underlining the significance of an increased risk of self-harm and suicidal behaviors in those individuals and the comorbidity of psychiatric disorders in enabling clinicians to discern specific areas to observe. Although there is limited evidence on effective protocols for PLE management, various treatment approaches are explained. Despite increased research on PLEs in recent years, further investigation is needed to fully understand the nature of PLEs and to optimize therapeutic strategies. This article consolidates the current knowledge by synthesizing information on PLEs, including risk factors, comorbidities, treatments, and their impact on individual's lives.

Background: The number of infants born via cesarean section (CS) is increasing globally due to medical and cultural reasons.

Objectives: This study aimed to determine the effect of the mode of delivery on early lung aeration in newborns using electrical impedance tomography (EIT).

Material and methods: The case-control study was conducted from December 2020 to April 2021. It included 32 term neonates delivered by CS and 20 term neonates delivered by normal vaginal delivery (NVD) as controls. Electrical impedance tomography examinations were performed with a Swisstom BB2 device with NEO SensorBelt and 32 integrated electrodes at 47.68 Hz. Three data recordings were conducted within 30, 60 and 90 min (mean times: 13, 62 and 93 min, respectively) after the birth.

Results: Cesarean section neonates, compared to those delivered by NVD, had greater non-aerated areas in gravity-dependent lung regions at the 2nd recording (p = 0.04). The CS group showed lower changes in lung stretch at the 2nd and 3rd recording compared to the NVD group (p = 0.022 and p = 0.032, respectively). In the study group, lung regions with the lowest stretch (10-20%, 20-30% and 30-40%) corresponded with increased total lung capacities 1 h after birth compared to the control group (p = 0.024, p = 0.004 and p = 0.044, respectively). Measurements from the 1st and 3rd EIT recording showed a greater distribution of tidal volume (TV) in the right lung toward the central regions among CS neonates compared to NVD neonates, whereas NVD neonates showed increased distribution of TV toward the central-ventral regions of the right lung immediately after birth.

Conclusions: The mode of delivery significantly affects early postnatal lung aeration in term neonates assessed using EIT. Caesarean section neonates were characterized by poorer aeration in gravity-dependent lung regions, whereas NVD neonates demonstrated greater changes in lung stretch and more intense tissue expansion, potentially leading to better postnatal adaptation.

Background: Vitamin D supplementation could offer irritable bowel syndrome (IBS) patients significant improvements in terms of symptom severity and overall quality of life (QoL). Yet, the potential benefits and risks associated with vitamin D supplementation still require additional investigation.

Objectives: We aimed to evaluate the impact of vitamin D supplementation on IBS using a systematic review and meta-analysis.

Material and methods: A comprehensive search was carried out utilizing 4 electronic databases (PubMed, Embase, Scopus, and Cochrane Library) to identify articles published in English-language peer-reviewed journals. The odds ratios (ORs), risk ratios (RRs) and mean differences (MDs), along with their respective 95% confidence intervals (95% CIs), were computed. Heterogeneity was evaluated using the appropriate p-value and Cochrane Q and I2 statistics. For the analysis, RevMan 5.3 was utilized.

Results: Nine randomized controlled trials involving a total of 780 participants were included in this study. Vitamin D supplementation, in adolescents and young adults with IBS, improves the IBS symptoms severity score, QoL and serum 25(OH)D levels compared to controls. We obtained an OR of 2.34 (95% CI: 1.56-3.50) for change in the IBS severity scoring system (IBS-SSS), OR = 2.51 (95% CI: 1.71-3.70) for change in QoL, low risk of any adverse events (RR 0.49 (95% CI: 0.35-0.69)), and substantial changes in serum 25(OH)D level (MD = 11.29 (95% CI: 7.13-15.45)). Results were statistically significant (p < 0.05).

Conclusion: Vitamin D supplementation could lead to better IBS management with a low risk of adverse events.

Background: Psychosocial interventions encompass psychotherapy and psychological education that explicitly target psychosocial adaptation. These interventions have been shown to have a substantial positive effect on reducing anxiety and depression, as well as improving overall quality of life (QoL). Nevertheless, there is still no consensus concerning the therapeutic effectiveness of these interventions.

Objectives: An umbrella review of systematic reviews and meta-analyses was conducted to determine the efficacy of psychological interventions in improving the QoL and psychological wellbeing of patients with cancer and mental illness.

Material and methods: A comprehensive literature search was conducted across multiple databases, namely PubMed, Embase, Scopus, and Cochrane Library. Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) was used to evaluate research methodological rigor.

Results: The 12 papers analyzed in this umbrella review explored psychological therapy for cancer and psychiatric patients. The included reviews covered in total 8,198 studies. The AMSTAR-2 rated 8 of 12 studies as high-quality and 4 as intermediate. A total of 369 studies examined cancer, 166 schizophrenia and 165 psychoses. Psychological therapy improved the QoL for cancer, schizophrenia and psychosis by 1.87, 1.48 and 1.61, respectively. Psychiatric and cancer patients have anxiety, sleep issues and a lower QoL. This umbrella study showed that psychological interventions improved QoL in both groups of patients.

Conclusion: Psychological therapy appears to improve cancer and mental illness patients' QoL and wellbeing. Most evidence is from highand middle-income nations. Therefore, further high-quality research that covers a larger geographical area and rigorous systematic reviews with complete meta-analyses is needed to gain useful insights in this field.

Background: The skin, with its robust structural integrity and advanced immune defense system, serves as a critical protective barrier against environmental toxins and carcinogenic compounds. Despite this, it remains vulnerable to the harmful effects of certain hazardous agents.

Objectives: This study aimed to investigate the chemopreventive potential of β-caryophyllene (BCP) in mitigating 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin carcinogenesis, focusing on the modulation of apoptosis and PI3K/AKT signaling pathways.

Material and methods: Swiss albino mice were utilized to assess the preventive effects of BCP in DMBA-induced skin cancer. Skin carcinogenesis was initiated by topical DMBA application, followed by promotion using croton oil. To evaluate the chemopreventive efficacy of BCP, a 50 mg/kg oral dose was administered 3 times a week for 16 weeks.

Results: The BCP treatment in DMBA-induced skin cancer mice significantly reduced tumor incidence, tumor burden and the total number of papillomas compared to untreated DMBA-exposed mice. Notably, BCP administration (p < 0.05) resulted in a marked increase in body weight and improvement in antioxidant enzyme activity. Additionally, BCP treatment led to significant reductions in lipid peroxidation and enhanced detoxification enzyme function. Histological examination of DMBA-induced skin tissues revealed the presence of keratin pearls, well-differentiated tumor cells and neutrophil infiltration. In contrast, BCP-treated mice showed only mild hyperplasia, dysplasia and moderate keratosis, suggesting a lower degree of tissue damage. Furthermore, BCP demonstrated a protective effect on liver histology, counteracting the toxic effects of DMBA exposure. Gene expression analysis revealed that BCP treatment significantly (p < 0.05) upregulated the pro-apoptotic genes Bax, p53, caspase-3 and caspase-9, while downregulating the anti-apoptotic Bcl-2 expression. Additionally, BCP treatment led to a marked reduction in the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and PI3K/Akt signaling pathways, which are key regulators of cell proliferation and survival.

Conclusions: This study provides compelling evidence that the antioxidant and pro-apoptotic effects of β-caryophyllene contribute to its chemopreventive properties in DMBA-induced skin carcinogenesis in mice. The modulation of key apoptotic signaling pathways and the suppression of the PI3K/Akt pathway by BCP underscores its potential as a therapeutic agent for preventing skin cancer. These findings pave the way for further exploration of BCP as a promising candidate for skin cancer prevention and therapy.

Background: Leukemia may form at any age, from newborns to the elderly, and accounts for considerable mortality worldwide.

Objectives: Nerolidol (NRD) is isolated from the aromatic florae oils and was found to have anticancer activities. However, the role of NRD in antiproliferative and apoptosis actions in acute lymphoblastic leukemia (ALL) is unclear.

Material and methods: Human ALL cell lines, MOLT-4, were used to examine the potential anticancer mechanisms of NRD on cellular proliferation, reactive oxygen species (ROS)-mediated apoptosis, oxidative stress markers, caspases, PI3K/AKT, nuclear factor kappa B (NF-κB), and STAT-3/VEGF/Bcl-2 signaling pathways.

Results: The MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay demonstrated that NRD inhibited MOLT-4 cell proliferation in a concentration-dependent manner, with an IC50 value of 30 μM. It was found that NRD (20 and 30 μM/mL) resulted in accumulated intracellular ROS, reduced oxidative stress and loss of mitochondrial membrane potential (MMP) in MOLT-4 cells in a concentration-related way. Nerolidol was able to induce apoptosis, as evidenced by dual acridine orange/ethidium bromide (AO/EB) staining. The levels of antioxidants, caspases-3, -8 and -9 were enhanced by NRD. This research proves that NRD instantaneously triggers ROS-mediated pro-apoptotic signaling and caspases and attenuates PI3K/Akt/NF-κB and STAT3/VEGF/Bcl-2 anti-apoptotic signaling.

Conclusions: Our results suggest that NRD treatment stimulates apoptosis in MOLT-4 cells by causing the accumulation of intracellular ROS through PI3K/AKT/STAT-3 signaling pathways.

Systemic lupus erythematosus (SLE) is a chronic, autoimmune inflammatory disease with a multisystem manifestation and a variety of clinical symptoms. Over the last decades, the prognosis and life expectancy of patients with SLE improved significantly due to the implementation of corticosteroids combined with immunosuppressive agents. Nevertheless, the use of these medications is often associated with the occurrence of serious side effects and additional deterioration of organ function. Therefore, developing and implementing novel therapies that are both safer and more effective in managing disease is crucial. For a long time, European Alliance of Associations for Rheumatology (EULAR) recommended only 2 biological agents in the treatment of SLE: belimumab and rituximab. However, in 2023, anifrolumab, an interferon (IFN) receptor inhibitor, and voclosporin, a novel calcineurin inhibitor, appeared in new SLE treatment guidelines. In addition, several biological agents are targeting different cells or cytokines that are being evaluated in phase II and III clinical trials. Apart from that, experimental therapies such as targeting of plasma cells, chimeric antigen receptor T-cell therapy (CAR-T) or stem cell transplantation appear promising in the treatment of the severe forms of SLE.

Background: Most patients with chest wall deformities have a negative body image, which affects their self-esteem and quality of life (QoL).

Objectives: The aim of this study was to evaluate changes in patients' QoL after minimally invasive repair of pectus excavatum (MIRPE).

Material and methods: A prospective, single-center study was conducted between 2019 and 2023. We included 20 pediatric patients at a median age of 15 years and 9 months who underwent MIRPE. Two QoL questionnaires were used: the KIDSCREEN-52 and the EQ-5D-Y. The data were statistically analyzed with the Wilcoxon and Mann-Whitney tests. All patients and their parents were asked to complete questionnaires preoperatively and 12 months after surgical treatment.

Results: All patients were followed up during the 12-month study period. The study group was comprised of 65% male patients. The median Haller index was 5.0 standard deviation (SD) = 1.58). The assessment of general health condition was higher among the boys (with postoperative improvement), though this finding was not statistically significant. Routine daily activities were easier for all patients after MIRPE (p = 0.048). The patients showed improved physical activity (p = 0.038) and psychological wellbeing (p = 0.013) after elevation of the anterior chest wall. There was no impact on relations with parents, free time or school environment, but we found better patient contact with peers in the postoperative period. A high correlation was confirmed between the parents' and the patients' responses in each questionnaire.

Conclusions: Chest wall deformities can have a strong impact on the patient's wellbeing, which is a very important part of psychological development in adolescents. Our study showed that improved QoL should be always considered as an indication for surgical treatment of chest wall deformities in children.