Discovery medicine最新文献

Gastric ulcers induced by non-steroidal anti-inflammatory drug (NSAID) usage have become a common public health problem, and several studies have established chronic NSAID usage to be one of the risk factors for the pathogenesis of peptic ulcers in patients. This review includes numerous articles that link NSAID usage with peptic mucosal erosion, especially among patients under anticoagulant therapy or with other risk factors. Risk factors for NSAID-induced peptic ulcers are reviewed, in addition to pathogenesis, clinical signs, symptoms, diagnosis, prevention, and treatments. We also emphasize effective methods for the prevention and management of peptic ulcers among NSAID users. Such methods include the use of selective Cyclo-oxygenase (COX-2) inhibitors as an alternative to aspirin or other Cyclo-oxygenase (COX-1) inhibitors, or using the lowest dosage possible in patients with other comorbidities. We have conducted a thorough review of the literature on diagnostic tests and alternative medication that can be used in the management of NSAID toxicity-induced ulcers.

Background: The feeble plasticity of spinal cord microvascular endothelial cells (SCMECs) after trauma is one of the major causes of spinal cord injury (SCI). Neural stem cells (NSCs) play an important role in nerve repair. Glycoprotein nonmetastatic B (GPNMB) has neuroprotective effects and can be stimulated by endothelin 1 (ET-1), and its expression is upregulated in SCI. Here, we aim to investigate whether elevated ET-1 levels stimulate NSCs to secrete GPNMB, thereby further promoting angiogenesis.

Methods: Mouse SCMECs and NSCs were isolated, cultured, and identified by flow cytometry and immunofluorescence staining. NSCs were treated with ET-1, while SCMECs were cocultured with NSCs, followed by treatment with ET-1. NCS and SCMEC viability were evaluated using cell counting kit 8 (CCK-8) assay, while cell proliferation, migration, invasion, and angiogenesis were examined using 5'-Ethynyl-2'-Deoxyuridine (EdU) staining, wound healing assay, Transwell assay, and tube formation assay. GPNMB expression in NCSs and SCMECs was quantified by western blot assay, quantitative Real-Time polymerase chain reaction (qRT-PCR), or enzyme-linked immunosorbent assay (ELISA).

Results: Mouse SCMECs and NSCs were successfully isolated and cultured. ET-1 promoted NSC viability and proliferation and upregulated GPNMB expression. NSCs and ET-1-treated NSCs promoted the viability, migration, invasion, angiogenesis, and GPNMB expression in SCMECs compared with control group cells, while GPNMB antibody reversed the above effects of ET-1 on the SCMECs.

Conclusion: ET-1 promotes SCMEC migration and invasion, along with angiogenesis, by enhancing NSC-mediated GPNMB secretion, so ET-1 may be a novel therapeutic target for SCI.

Aging is frequently associated with a progressive increase in chronic low-grade inflammation, known as "inflammaging". Numerous studies have shown that inflammaging is closely linked to the development of several age-related diseases. However, the underlying mechanism and its causal role are still not fully understood despite this association. In the complex context of aging, mesenchymal stem cells (MSCs) undergo changes in behavior and functionality. This narrative topical review examines the recent advances in aging research, specifically focusing on the role of inflammaging and related mechanisms that contribute to age-related chronic diseases. The authors critically investigated whether and how inflammaging, epigenetic damage, mitochondrial changes, and macrophage alterations may influence stem cell behavior, highlighting the interplay between these factors and their potential therapeutic implications. By elucidating the mechanisms underlying these processes, we can gain valuable insights into the maintenance and regeneration of stem cell populations, providing the basis for novel therapeutic strategies targeting age-related decline and disease progression.

The study of chromosomal shape, characteristics, and behavior in somatic cell division (mitosis) during growth and development and in germ cell division (meiosis) during reproduction is known as cytogenetics. Many techniques can be used for cytogenetics, including fluorescent in situ hybridization (FISH), spectral karyotyping (SKY), multicolor FISH (M-FISH), microarray, and optical genome mapping (OGM). OGM is a novel genome-wide method that can identify structural variants (SVs) and copy number variants (CNVs) with only one test. Genomic structural information that is difficult to obtain with DNA sequencing can be promptly obtained with OGM, in which large molecule lengths can be mapped at a reasonable cost. OGM is increasingly being used to investigate chromosome abnormalities in genetic disorders and human cancer, but it was first utilized in genome assembly and research. According to recent research, OGM is capable of identifying every clinically significant variation seen in trials using conventional care. OGM is being utilized to identify genomic abnormalities in patients with malignancies and constitutional illnesses. It is regarded as a revolution in the field of cytogenetics. Rather than sequencing DNA, OGM relies on DNA labeling. Currently, the OGM technique with the Saphyr system from Bionano Genomics is a widely utilized platform for cytogenetic analysis. In conclusion, OGM can now be considered a highly reliable method for the identification of chromosomal abnormalities in the diagnosis of tumors and hematological diseases.

Background: Tumor necrosis factor alpha induced protein 3 (TNFAIP3) is reportedly to have significant implications for autophagy regulation in various cancers. The current study aimed to decipher the role and mechanism of TNFAIP3 in diffuse large B-cell lymphoma (DLBCL) by modulating autophagy.

Methods: Information pertaining to the differential expression and prognostic role of TNFAIP3 in DLBCL was gleaned from the Gene Expression Omnibus (GEO) database. The TNFAIP3 expression levels in human DLBCL cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Cell counting kit-8 (CCK-8) and colony formation assays were employed to determine cell proliferation. Transwell assay and flow cytometry were applied to detect cell migration and apoptosis, respectively. Immunofluorescence and transmission electron microscope were used for the assessment of cell autophagy. The levels of apoptotic markers (caspase-3, cleaved-caspase-3, Bcl-2 Associated X (Bax), and B cell lymphoma-2 (Bcl-2)), autophagy indicators (the ratio of microtubule-associated proteins 1A/1B light chain 3 II and I (LC3II/LC3I), Sequestosome (p62)), and pathway proteins (toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), Transcription Factor NF-Kappa-B P65 Subunit (p65), and phosphorylated-p65 (p-p65)) were assessed via Western blotting. Immunohistochemistry was employed to detect Ki67 expression in tumor tissues.

Results: TNFAIP3 expression in DLBCL samples was downregulated, correlating with poor prognosis. TNFAIP3 expression was also downregulated in DLBCL cells. It was found that TNFAIP3 impeded cell proliferation and migration, and enhanced apoptosis of OCI-LY3 cells. Intervention with autophagy inhibitor 3-methyladenine (3-MA) markedly reversed apoptosis of OCI-LY3 cells induced by TNFAIP3. Besides, TNFAIP3 induced autophagy via modulating the TLR4/MyD88/nuclear factor kappa B (NF-κB) signaling pathway. In vivo experiments showed that TNFAIP3 expression in DLBCL was downregulated, and upregulation of TNFAIP3 could inhibit tumor growth.

Conclusion: TNFAIP3 inhibits DLBCL progression by inducing TLR4/MyD88/NF-κB pathway-mediated autophagy.

Background: Aciclovir, often known as acyclovir, is a nucleoside analog that exhibits antiviral activity in vitro against human herpesvirus 6 (HHV-6), cytomegalovirus (CMV), varicella-zoster virus (VZV), and herpes simplex virus (HSV). Valacyclovir is an amino acid ester prodrug of acyclovir. We examined valacyclovir, which is also an anti-viral agent, for its effects on inflammation.

Methods: Mammalian Macrophages were activated by lipopolysaccharide (LPS) in the presence of a concentration range of Valacyclovir. Tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-12p40 enzyme-linked immunosorbent assay (ELISA) was performed to measure the production levels of these pro-inflammatory cytokines.

Results: Our results suggest that Valacyclovir had anti-inflammatory activity on the LPS-activated mammalian macrophages.

Conclusion: Valacyclovir has the potential to be utilized in the clinical setting as an anti-viral drug molecule with anti-inflammatory properties. Future studies are needed to further confirm its activities on different immune system cell types.

Background: Bile duct injury (BDI) is a severe complication following cholecystectomy and is therefore a particularly concerning surgical predicament for hepatobiliary surgeons. Owing to very high medical compensation awarded to patients suffering from BDI, surgeons need to exercise caution during surgery to avoid BDI. Herein, we explored a novel method to identify cystic duct during laparoscopic cholecystectomy (LC), expanding the applicability of this surgical approach.

Methods: Patients receiving LC between April 2021 and October 2022 at the Gaoyou People's Hospital were included in this retrospective clinical study and divided into two groups according to whether the cystic duct was incised (one group with LC alone, while another with laparoscopic cholecystectomy and cystic duct exploration [LCCDE]). Clinical and baseline characteristics of patients were collected, and the preoperative and postoperative biochemical parameters were compared. The surgical outcomes of LCCDE were observed.

Results: A total of 114 patients had undergone LC, while 162 patients had received LCCDE as treatment. There were no significant differences in age, gender, common bile duct diameter, preoperative and postoperative biochemical parameters between the two groups. No significant difference in the mean operation time between the LC and LCCDE groups was noted (p = 0.409). In the LCCDE group, white secretions in the cystic duct were observed in 92 patients (56.8%).

Conclusions: The presence of intraoperative white secretions in the cystic duct may further confirm the presence of cystic duct, thereby enabling earlier detection of BDI. Importantly, LCCDE, as the new surgical method explored in this study, does not extend the operation time.

Background: Atrial fibrillation (AF) is the most common type of arrhythmia. Heart rate variability (HRV) may be associated with AF risk. The aim of this study was to test HRV indices and arrhythmias as predictors of paroxysmal AF based on 24-hour dynamic electrocardiogram recordings of patients.

Methods: A total of 199 patients with paroxysmal AF (AF group) and 204 elderly volunteers over 60 years old (Control group) who underwent a 24-hour dynamic electrocardiogram from August 2022 to March 2023 were included. Time-domain indices, frequency-domain indices, and arrhythmia data of the two groups were classified and measured. Binary logistic regression analysis was performed on variables with significant differences to identify independent risk factors. A nomogram prediction model was established, and the sum of individual scores of each variable was calculated.

Results: Gender, age, body mass index and low-density lipoprotein (LDL) did not differ significantly between AF and Control groups (p > 0.05), whereas significant group differences were found for smoking, hypertension, diabetes, and high-density lipoprotein (HDL) (p < 0.05). The standard deviation of all normal to normal (NN) R-R intervals (SDNN), standard deviation of 5-minute average NN intervals (SDANN), root mean square of successive NN interval differences (rMSSD), 50 ms from the preceding interval (pNN50), low-frequency/high-frequency (LF/HF), LF, premature atrial contractions (PACs), atrial tachycardia (AT), T-wave index, and ST-segment index differed significantly between the two groups. Logistic regression analysis identified rMSSD, PACs, and AT as independent predictors of AF. For each unit increase in rMSSD and PACs, the odds of developing AF increased by 1.0357 and 1.0005 times, respectively. For each unit increase in AT, the odds of developing AF decreased by 0.9976 times. The total score of the nomogram prediction model ranged from 0 to 110.

Conclusion: The autonomic nervous system (ANS) plays a pivotal role in the occurrence and development of AF. The individualized nomogram prediction model of AF occurrence contributes to the early identification of high-risk patients with AF.

Background: Severe neonatal hyperbilirubinemia can cause hearing impairment. Bilirubin can be deposited in nerve cells, and the brainstem and the 8th nerve are especially sensitive to bilirubin toxicity. Abnormal changes in brainstem auditory evoked potential (BAEP) can be observed, and the BAEP test measures a nerve potential induced by short, high-frequency sound stimulation; thus, it is able to detect damage to the auditory conduction pathway in children. We aimed to identify relationships between clinical features and BAEP abnormalities in children with hyperbilirubinemia and to assess the predictive power of these risk factors for bilirubin-induced neurological damage.

Methods: Children with hyperbilirubinemia were evaluated with BAEP and retrospectively enrolled in the study between January 2012 and December 2018. Multivariate logistic regression was performed to identify independent predictors of BAEP abnormalities.

Results: Of the 561 children with hyperbilirubinemia enrolled, the BAEP anomaly group accounted for 198 (35.3%) cases. Except for body weight, there were no significant differences in the general data between the two groups with hyperbilirubinemia (p > 0.05). Univariate analysis showed that prematurity, abnormal umbilical cord, and gestational diabetes during pregnancy were significantly correlated with abnormal BAEP. Multivariate logistic regression analysis identified prematurity (p = 0.001), gestational diabetes (p = 0.03), Premature rupture of membranes (p = 0.013), total serum bilirubin (TSB), bilirubin/albumin (B/A) as independent risk factors for BAEP abnormalities. The prediction accuracy of TSB (Area Under Curve (AUC) = 0.557) and B/A (AUC = 0.566) was low, indicating that abnormal BAEP should be detected by multiple factors.

Conclusions: Multivariate detection is beneficial for predicting the occurrence of auditory nerve injury in patients with hyperbilirubinemia.

Background: Remodeling of vascular smooth muscle cells (VSMCs), as a pathological hallmark of cardiovascular diseases, is related to the molecular rewiring of Calcium signaling, which induces upregulation of stromal interaction molecule (STIM) proteins. This study analyzed the influence of STIM1 proteins on the remodeling of VSMCs in atherosclerosis (AS).

Methods: After oxidized low-density lipoprotein (ox-LDL) treatment and transfection, VSMC viability, migration, and invasion were separately measured using Cell Counting Kit-8, Scratch assay, and Transwell assay. An animal AS model was constructed, and histological analysis via hematoxylin-eosin staining was conducted on the aorta.

Results: Ox-LDL promoted expression of STIM1 and Orai calcium release-activated calcium modulator 1 (Orai1). STIM1 or Orai1 downregulation suppressed viability, migration, invasion, and phenotypic switching of ox-LDL-treated VSMCs, whereas STIM1 or Orai1 upregulation had opposite effects. Orai1 level was upregulated by STIM1 overexpression. Orai1 silencing reversed the effects of STIM1 overexpression in VSMCs. STIM1 deficiency alleviated AS and regulated expression of Orai1 and phenotypic switch-related factors in vivo.

Conclusion: STIM1 deficiency suppresses viability, migration, invasion, and phenotypic switching of ox-LDL-induced VSMCs and alleviates AS by inhibiting Orai1.