Biomedical reports最新文献

Hyperinflammation is one of the most important pathophysiological risk factors for poor prognosis in patients with coronavirus disease-2019 (Covid-19). Low vagal neuro-immune modulation can lead into this kind of immune dysregulation. The association between vagal activity, sex and inflammatory markers were investigated in patients with Covid-19. A total of 19 patients with Covid-19 were included in the present study. Vagus nerve activity was indexed by heart rate variability (HRV) derived from electrocardiogram at hospital admission. Linear HRV parameters included the root mean square of successive RR interval differences (RMSSD) and high-frequency HRV (HF-HRV), while non-linear parameters included 2 UV%. Immune/inflammatory parameters included C-reactive protein (CRP), interleukin-6 (IL-6), neutrophil/lymphocyte ratio (NLR), systemic inflammatory index (SII), and procalcitonin (PCT). It has been revealed that both linear HRV indices HF-HRV and RMSSD, are significantly negatively correlated with CRP and IL-6, independent of age. The non-linear index of 2 UV% is significantly negatively correlated with NLR and SII, which reflect subtle changes in the response of immunocompetent cells. Patients that received high-flow nasal oxygen therapy had significantly higher IL-6 and CRP levels and lower levels of HF-HRV and RMSSD. These patients also had a significantly longer length of stay in hospital (LOS) than patients receiving low-flow oxygen therapy. Men had higher plasma PCT levels and longer LOS in hospital than women, and PCT statistically explained (mediated) the association between sex and LOS. The present study showed different correlations of linear and non-linear vagal indexes of HRV and inflammatory markers in patients with Covid-19. Significant sex differences in certain inflammatory markers were also observed, which may very well verify previous findings of poor prognosis in men with Covid-19. HRV reflects a continuous interaction between the sympathetic and parasympathetic autonomic nervous systems, which are affected by mental or physical stress, and certain disease states. The increased sympathetic and decreased parasympathetic vagal tone contribute to a higher risk of diseases associated with inflammation, cardiovascular disease, cancer, pulmonary diseases and other pathologies, including infectious diseases such as Covid-19. The present study showed that higher RMSSD (a marker of vagal activity) in Covid-19 patients is associated with lower levels of inflammatory biomarkers, a lower need for treatment and is negatively correlated with intensive care unit admission, leading to a shorter hospital stay. These findings support the idea that activation of vagus nerve may help certain Covid-19 patients by reducing the cytokine storm and excessive inflammation.

Leptin receptors (LEPR) are located in the central nervous system and other tissues including adipocytes and endothelial cells, where they play a key role in mediating the effects of leptin. MicroRNA (miR/miRNA)-27a and miR-155 have been shown to play an important role in the regulation of LEPR expression and are differentially expressed in various diseases. Therefore, the present study analyzed potential associations of LEPR deletion/insertion (Del/Ins), miR-27aA>G (rs895819) and miR-155T>A (rs767649) polymorphisms with a predisposition to hypertension (HTN). Genotyping was performed by a PCR-restriction fragment length polymorphism assay. Frequencies of LEPR Del/Ins and miRNA gene polymorphisms in patients diagnosed with HTN (n=232) and randomly selected healthy controls (n=247) were assessed. The present study found that Del/Ins and Ins/Ins genotypes and the Ins allele of the LEPR Del/Ins polymorphism were associated with a decreased risk of HTN compared with controls, whereas the miR-27aA>G rs895819 polymorphism was associated with an increased risk of HTN. Combined genotype and allele analyses for LEPR Del/Ins and two miRNA polymorphisms revealed an association with an increased risk or a decreased risk of HTN. Furthermore, stratification analysis revealed that HTN risk factors were associated with waist circumference (WC) and high-density lipoprotein cholesterol (HDL-C) values in LEPR Del/Ins polymorphism. They were also associated with body mass index, WC, triglyceride and HDL-C values in miR-27aA>G polymorphism. The present study revealed a combined effect of LEPR Del/Ins and miR-27aA>G polymorphisms on the risk of HTN in Koreans, suggesting that these gene polymorphisms could be potential markers for predicting HTN risk.

Previous studies have determined that aberrant expression of the fas-associated death domain (FADD) contributes to the development of cancer. However, no pan-cancer analysis has been reported to explore the relationship between FADD and various cancers. Multiple databases were screened to identify cancer datasets for the present study and to validate the expression of FADD in various tumors. The association of FADD alteration with cancer prognosis, clinical features and tumor immunity was also evaluated. Reverse transcription-quantitative PCR (RT-qPCR) was utilized to confirm the expression of FADD in breast, colon, liver and gastric cancer cells. Analysis of Gene Expression Omnibus database and The Cancer Genome Atlas database indicated that FADD was highly expressed in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma, cholangiocarcinoma, colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD) and prostate adenocarcinoma, whereas RT-qPCR results revealed that FADD was highly expressed in breast cancer and colon cancer. Further analyses demonstrated that FADD expression was significantly altered in ESCA, head and neck squamous cell carcinoma (HNSC), lung squamous cell carcinoma and BRCA. FADD expression was observed to be a risk factor of the overall survival in patients with HNSC, LIHC and LUAD as demonstrated by Kaplan-Meier and Cox regression analyses. The results of the present study demonstrated that FADD is highly expressed in numerous malignancies and can be utilized as a biomarker for the diagnosis of BRCA, COAD, LIHC and stomach adenocarcinoma. Moreover, FADD expression is a predictive risk factor for the development of HNSC, LIHC and LUAD and can potentially be used as a prognostic marker for these cancers.

During the COVID-19 pandemic, ~10% of the global population was officially affected, resulting in diverse changes, ranging from shopping habits to stringent hospital protocols. This article sought to provide a concise summary of relevant data concerning the interplay between COVID-19 and trauma, encompassing the entire trajectory from presentation to hospital discharge. Throughout the pandemic, there was a noticeable reduction in trauma presentations, while the ranking of injury mechanisms remained largely unchanged. To ensure essential surgical support, protocols were adjusted accordingly. Although there were some less significant changes in injury severity score, hospital length of stay, intensive care unit stay and mortality, the overall patient outcomes appeared to improve. In conclusion, the COVID-19 pandemic led to a decline in trauma cases and an enhancement in patient outcomes. However, regrettably, certain mechanisms of injury saw an increase in frequency. To cope with the epidemiological context, management strategies were adapted, and unutilized resources were redirected to cater to the care of COVID-19 patients.

Soft tissue sarcomas (STS) are very rare tumors, accounting for <1% of all malignancies. Leiomyosarcoma (LMS), accounts for 10-20% of STS. Gastric metastasis of LMS is extremely rare, and only a few cases have been reported. In the present report, two clinical cases of LMS with gastric metastasis. In the present cases, the metastases presented as a solitary lesion and was located in the upper body anterior wall in case 1, and body-greater curvature in case 2. It is debatable whether to perform any local treatment for gastric metastasis due to its poor prognosis. However, the progression of metastatic cancer in the stomach can lead to gastric bleeding, abdominal pain, and dysphagia, which may further shorten survival and decrease a patient's quality of life. Therefore, metastasectomy was performed in the present cases. This should be considered if digestive tract symptoms occur during the treatment of LMS.

The purpose of the present study was to assess the prevalence of Ureaplasma urealyticum (U. urealyticum), Mycoplasma hominis (M. hominis) and Chlamydia trachomatis (C. trachomatis) in a Romanian population considering the presence or absence of genital symptoms. Urethral and vaginal samples were collected from patients presenting at 'Ponderas' Academic Hospital (Bucharest, Romania) from January 2021 to December 2021. A total of 266 samples were obtained from two groups of patients: Symptomatic subjects with urethritis, prostatitis, vaginitis or both urethritis and prostatitis (n=59; 22%), and asymptomatic subjects (n=207; 78%). Mycoplasma and Chlamydia kits were used to assess the presence of U. urealyticum and M. hominis, and C. trachomatis, respectively. The symptomatic subjects comprised 27 patients with urethritis symptoms, of whom 4 (15%) were infected with U. urealyticum and 1 (4%) was infected with C. trachomatis. In addition, 23 (9%) of the patients had prostatitis-like symptoms, which in 3 (13%) of the patients was associated with U. urealyticum and in 1 patient (4%) was associated with C. trachomatis. None of the symptomatic patients were infected with M. hominis. By contrast, 29 (14%) of the asymptomatic patients were discovered to be infected with U. urealyticum, 13 (6%) were coinfected with both Mollicutes and 4 (2%) were infected with C. trachomatis; only 1 patient was positive for M. hominis alone. Two patients (14%) who presented with U. urealyticum and M. hominis coinfection were also infected with C. trachomatis. No patient with U. urealyticum or M. hominis alone was also positive for C. trachomatis. Therefore, the most frequently identified pathogen populating the genital tract in both males and females was U. urealyticum, followed by coinfection with U. urealyticum and M. hominis, and C. trachomatis. As these infections are asymptomatic in numerous cases, this suggests that a thorough screening should be mandatory.

Suppression of the antitumor cytokine interleukin-24 (IL-24) is critical for the survival of myxoid liposarcoma (MLS) cells. It has been previously demonstrated by the authors that an MLS-specific chimeric oncoprotein, translocated in liposarcoma-CCAAT/enhancer-binding protein homologous protein (TLS-CHOP), supresses IL24 mRNA expression via induction of proteoglycan 4 (PRG4) to sustain MLS cell proliferation. However, IL-24 has also been revealed to be suppressed by the ubiquitin-proteasome system in human ovarian and lung cancer cells. Therefore, the aim of the present study was to elucidate the mechanism of IL-24 suppression in MLS cells. The results revealed that the proteasome inhibitor, MG-132, induced cell death in MLS cells in vitro; this effect was reduced following IL-24 knockdown. This indicated that proteasomal degradation of IL-24 may be an important process for MLS cell survival. In addition, it was also previously revealed by the authors that knockdown of plasminogen activator inhibitor-1 (PAI-1), a TLS-CHOP downstream molecule, suppressed the growth of MLS cells, thus instigating the investigation of the effect of PAI-1 on IL-24 expression in MLS cells. Double knockdown of PAI-1 and IL-24 negated the growth-suppressive effect of PAI-1 single knockdown in MLS cells. Interestingly, PAI-1 single knockdown did not increase the mRNA expression of IL24, but it did increase the protein abundance of IL-24, indicating that PAI-1 suppressed IL-24 expression by promoting its proteasomal degradation. Moreover, treatment of MLS cells with a PAI-1 inhibitor, TM5275, induced IL-24 protein expression and apoptosis. Collectively, the results of the present as well as previous studies indicated that IL-24 expression may be suppressed at the transcriptional level by PRG4 and at the protein level by PAI-1 in MLS cells. Accordingly, PAI-1 may represent an effective therapeutic target for MLS treatment.

Acquired hemophilia A (AHA) is a rare disease that results from factor VIII inhibitors causing abnormal coagulation, and certain cases may develop after highly invasive surgery. The present case study reports on a 68-year-old male patient who developed AHA after undergoing a subtotal stomach-preserving pancreatoduodenectomy for distal cholangiocarcinoma. The patient experienced complications after surgery, requiring reoperation on postoperative day (PD) 5 due to rupture of the Braun's enterostomy. On PD 6, angiography was performed after bleeding was detected in the jejunal limb, but hemostasis occurred spontaneously during the examination. Bleeding was observed again on PD 8 and direct surgical ligation was performed. On PD 14, bleeding recurred in the jejunal limb and angiography was performed to embolize the periphery of the second jejunal artery. During the procedure, the prothrombin time was normal, but only the activated partial thromboplastin time was prolonged. A close examination of the coagulation system revealed a decrease in factor VIII levels and the presence of factor VIII inhibitors, resulting in the diagnosis of AHA. Administration of steroids was initiated on PD 15 and, in addition to daily blood transfusions, activated prothrombin complex concentrate was administered to achieve hemostasis. The patient was discharged from the intensive care unit on PD 36 but later developed an intractable labial fistula due to suture failure at the gastrojejunostomy site. As the use of factor VIII inhibitors continued despite the administration of steroids, cyclophosphamide (CPA) pulse therapy was added at PD 58. However, CPA was ineffective and the administration of rituximab was initiated on PD 98. After 12 courses of rituximab, the patient tested negative for factor VIII inhibitors on PD 219. On PD 289, labial fistula closure was performed with continuous replacement of factor VIII and the patient was discharged on PD 342.

Members of the renin-angiotensin aldosterone system (RAAS) are expressed by various retinal tissues including Mueller glial cells. As the RAAS is hypothesized to play an important role in the pathogenesis of diseases that threaten vision, such as diabetic macular edema or retinal vein occlusion, the possible changes induced by exposure of the human cell line MIO-M1, an established model of Mueller cells, to angiotensin II or aldosterone for 6 h under hypoxic and/or hyperglycemic conditions were investigated. The mRNA expression levels of the members of the RAAS were assessed by reverse transcription-quantitative PCR, and the secretion of cytokines was assessed by ELISA. Under hyperglycemic conditions, the mRNA expression levels of the angiotensin-converting enzyme 2 (ACE2), angiotensin II receptors, AT₁ and AT₂, and the receptor of angiotensin (1-7) MAS1 were significantly higher after exposure to angiotensin II, and the expression of ACE2, AT₂, and IL-6 (a marker of inflammation) was significantly increased after treatment with aldosterone; the expression of the other targets investigated remained unchanged. Significantly more IL-6 was secreted by MIO-M1 cells exposed to hyperglycemia and angiotensin. When cells were cultured in a hypoxic environment, additional treatment with aldosterone significantly increased the mRNA expression levels of ACE, but significantly more ACE2 mRNA was expressed in the presence of angiotensin II. Under hypoxic plus hyperglycemic conditions, significantly less ACE but more AT₂ was expressed after treatment with angiotensin II, which also led to strongly elevated expression of IL-6. The mRNA expression levels of the angiogenic growth factor VEGF-A and secretion of the encoded protein were notably increased under hypoxic and hypoxic plus hyperglycemic conditions, irrespective of additional treatment with angiotensin II or aldosterone. These findings suggest that angiotensin II induces a pro-inflammatory response in MIO-M1 cells under hyperglycemic conditions despite activation of the counteracting ACE2/MAS1 signaling cascade. However, hypoxia results in an increased expression of angiogenic VEGF-A by these cells, which is not altered by angiotensin II or aldosterone.