Journal of Investigative Medicine最新文献

The A disintegrin and metalloprotease (ADAM) family is involved in many vital cellular events, from proliferation to migration, and accumulated evidence suggests its increased expression in malignant tumors. In this study, we investigated ADAM17 expression in non-small cell lung cancer (NSCLC) and its relationship with clinicopathological factors and survival. Immunohistochemical staining of ADAM expression was performed in 108 patients with NSCLC and in 54 control cases with no known malignant diagnosis. Association between ADAM17 expression, clinicopathological factors, and survival were analyzed. The Kaplan-Meier method was used for survival analysis. ADAM17 was lowly expressed in 89 (82.4%) and highly expressed in 19 (17.6%) of the patients with NSCLC. In univariate analysis, high ADAM17 expression, lymphovascular invasion, stage, and treatment response significantly affected progression-free survival (PFS) and overall survival (OS) (p < 0.05). Multivariate analysis also showed that high ADAM17 expression, lymphovascular invasion, stage, and treatment response were important prognostic factors for PFS and OS (p < 0.05). Our study revealed that high ADAM17 expression significantly associated with OS and PFS in patients with NSCLC. ADAM17 may potentially be the area of a new targeted treatment strategy in NSCLC. Thus, routine evaluation of ADAM17 expression in patients with NSCLC may be a future consideration.

Hepatocellular carcinoma (HCC) is a prevalent form of primary liver cancer with a 5-year survival rate of just 18%. Ferulic acid, a natural compound found in fruits and vegetables such as sweet corn, rice bran, and dong quai, is an encouraging drug known for its diverse positive effects on the body, including anti-inflammatory, anti-apoptotic, and neuroprotective properties. Our study aimed to investigate the potential antitumor effects of ferulic acid to inhibit tumor growth and inflammation of HCC in rats. HCC was induced in rats by administering thioacetamide. Additionally, some rats were given 50 mg/kg of ferulic acid three times a week for 16 weeks. Liver function was assessed by measuring serum alpha-fetoprotein (AFP) and examining hepatic tissue sections stained with hematoxylin/eosin or anti-hypoxia induced factor-1α (HIF-1α). The hepatic mRNA and protein levels of HIF-1α, nuclear factor κB (NFκB), tumor necrosis factor-α (TNF-α), mammalian target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3), cMyc, and cyclin D1 were examined. The results showed that ferulic acid increased the rats' survival rate by reducing serum AFP levels and suppressing hepatic nodules. Furthermore, ferulic acid ameliorated the appearance of vacuolated cytoplasm induced by HCC, reduced apoptotic nuclei, and necrotic nodules. Finally, ferulic acid decreased the expression of HIF-1α, NFκB, TNF-α, mTOR, STAT3, cMyc, and cyclin D1. In conclusion, ferulic acid is believed to possess antitumor properties by inhibiting HCC-induced hypoxia through the suppression of HIF-1α expression. Additionally, it helps in reducing the expression of mTOR, STAT3, cMyc, and cyclin D1, thereby slowing down tumor growth. Lastly, ferulic acid reduced hepatic tissue inflammation by downregulating NFκB and TNF-α.

The World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic on March 11, 2020. Since then, researchers have been investigating the efficacy and side effects of its medication, up until now. From the viewpoint of Persian medicine, some medications such as antihistamines may cause retention of secretions and lead to exacerbation and spread of the disease in the body. There are studies with conflicting results regarding the effectiveness of antihistamines in COVID-19. Systematic reviews found a lack of data on beneficial effect of antihistamine-decongestant-analgesic combinations for the common cold and a limited short-term effect of antihistamines on severity of overall symptoms. This prospective cohort study was designed to investigate the relationship between the use of antihistamines and the severity of COVID-19 symptoms. Three hundred patients with a diagnosis of COVID-19 participated in the study in Shiraz, Iran from December 4, 2021 until January 24, 2022. The interviews were conducted via phone call by a single interviewer. Patients were followed weekly for 4 weeks. We collected information by using a data collection form, containing demographic information, underlying disease, COVID-19 symptoms, treatment methods, medications, and a list of antihistamines and herbs that might have been used. Generalized estimating equations were applied to assess the relationship between the severity of COVID-19 and the use of antihistamines, taking into account potential confounding factors such as time and herbal consumption. The difference in the severity of COVID-19 disease in antihistamine users compared to nonusers was not significant in 4 weeks despite the higher baseline severity in nonusers. The comparison of two groups of antihistamine users and nonusers showed that there was a significant difference (p = 0.001) regarding the use of herbal medicines.

Atherosclerosis, a major cause of cardiovascular diseases, is characterized by the accumulation of oxidized lipoproteins (ox-LDL) within arterial walls, leading to inflammation and plaque formation. Hydrogen sulfide (H₂S) has demonstrated anti-inflammatory and vascular protective properties, but its role in modulating macrophage endocytosis of ox-LDL and its impact on early atherosclerosis development remains unclear. Macrophage cultures were utilized for ox-LDL uptake experiments. Macrophages were pretreated with sodium hydrosulfide (NaHS) (50 μmol/L) or propargylglycine (PPG, 3 mmol/L) for 1 h, followed by incubation with DiI-ox-LDL (10 μg/mL) for an additional 2 h. DiI-ox-LDL uptake was visualized using live-cell imaging. The expression of scavenger receptors CD36 and SR-A was assessed through immunofluorescent staining and western blot analysis. To determine the intracellular signal transduction pathways involved, macrophages were pretreated with NF-κB pathway blocker pyrrolidine dithiocarbamate or MAPK inhibitor PD98059 before the addition of NaHS. NaHS significantly inhibited ox-LDL uptake by macrophages, while PPG treatment markedly increased this process. Immunocytochemistry and western blot analysis revealed that the expressions of CD36 and SR-A were induced by ox-LDL but inhibited by NaHS in a concentration- and time-dependent manner. Furthermore, H₂S down-regulated ox-LDL receptors CD36 and SR-A through the NF-κB signal pathway. H₂S inhibits early atherosclerosis development by modulating macrophage uptake of ox-LDL through the down-regulation of CD36 and SR-A receptors via the NF-κB signaling pathway. These findings provide new evidence for the role of H₂S in atherosclerosis and its potential therapeutic value.

Forty-one families with multiple cases of de novo acute myeloid leukemia (AML), B-cell acute lymphocytic leukemia (B-ALL), or both are presented. The families were randomly collected from physicians, genetic counselors, and other sources. Medical records were collected and reviewed for all families. In 17 of the families, a parent and child with acute leukemia were identified; and in 15 of the pairs, the parent and child were of the same sex. Nine grandparent-grandchild affected pairs with AML-AML were identified, occurring in six families, and six of those pairs were also of the same sex. Anticipation was a common feature of these multigenerational pairs. Twenty families were identified with multiple siblings (none twins) with acute leukemia. This includes 16 sibling pairs and 4 sibling triples. The members of each sibling pair in the AML-AML group and in the B-ALL-B-ALL group were generally of roughly the same age. Curiously, this is not true of those in the AML-B-ALL group. Four of the 41 families had contributions to more than 1 family relationship category. Although inheritance in familial acute leukemia has usually been consistent with an autosomal dominant pattern, these data suggest that an X chromosome gene may be involved in some cases, perhaps in the pseudoautosomal region of the X chromosome as we have reported in familial Hodgkin lymphoma.

Clinical research is a key factor in healthcare progress, as it contributes toward improving our knowledge on the prevention, etiology, and treatment of different conditions. Healthcare professionals and researchers should be familiar with this specific terminology and procedures of clinical research to understand and be able to evaluate clinical trial results and make decisions using up-to-date recommendations. To do so, they must be familiar with different methodological aspects: from establishing the type of design, the study population, and the groups to be studied, to understanding the randomization and blinding processes. Additionally, when it comes to communicating the results and publishing them, it is also necessary to know how to do it adequately to ensure transparency. This work includes a description of different concepts commonly used in clinical research, particularly in the clinical trials field, in an attempt to compile different topics by providing a brief and accessible overview.

The effect of pre-hospital use of renin-angiotensin system (RAS) inhibitors (angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs)) on clinical outcomes of hypertensive patients with COVID-19 has been questioned due to conflicting reports on this issue. After applying exclusion criteria, 175 COVID-19 hospitalized patients admitted to the Tishreen Hospital from January 1 to July 31, 2021 were retrospectively enrolled in this study. Baseline characteristics and in-hospital mortality rate were assessed between hypertensive (N = 91, 52%) and non-hypertensive (N = 84, 48%) patients, as well as between patients taking ACEis/ARBs and non-ACEis/ARBs within the hypertensive group. A lower mortality rate (51.2 versus 31.9%, p = 0.009) was observed in the hypertensive group (mean age 64.6 years, 64.8% males) compared to the non-hypertensive (mean age 62.6 years, 66.7% males). Patients' mortality in the non-hypertensive group was associated with lower blood oxygen saturation (SPO2 = 75 versus 86%, p = 0.002), increased levels of inflammatory (CRP, white blood cell and neutrophils count), and tissue/renal injury markers (LDH, urea, and creatinine). In the hypertensive group, a lower mortality rate was noted in the ACEis/ARBs group compared to the non-ACEis/ARBs (24.1 versus 45.5%, p = 0.036), and this was associated with a decrease in D-DIMER levels, although not significant (1723 versus 2683 ng/mL, p > 0.05). Death in the non-ACEis/ARBs group was associated with decreased SPO2 and tissue/renal injury markers (LDH, CK, AST, urea, and creatinine). We concluded that hypertension is not a direct cause of poor prognosis in COVID-19 patients and that multi-organ damage is a significant indicator of death from COVID-19. RAS inhibitors could improve the survival of hypertensive COVID-19 patients.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease. Clinical manifestations include intravascular hemolysis, renal dysfunction, fatigue, jaundice, pulmonary hypertension, and so on. Renal injury, as a clinical feature of PNH, is difficult to diagnose and is one of the causes of death in patients with PNH. This article reviews the progress in research on PNH combined with renal injury to improve clinicians' understanding of renal injury in PNH patients, define and judge staging in a timely and accurate manner, enable patients to receive timely and appropriate treatment and reduce mortality.

Glucagon-like peptide-1 receptor agonist (GLP-1a) medications have been shown in randomized controlled trials (RCTs) to have consistent and impressive effectiveness in lowering hemoglobin A1c (HbA1c) and weight, but limited data exist on the efficacy of GLP-1a medications in clinical practice. We studied the association between GLP-1a therapy and changes in weight and HbA1c in a real-world patient population. In this retrospective cohort study of patients seen in a primary care clinic between 2012 and 2021, we examined the change in weight and HbA1c over 12 months in a cohort of patients with at least one prescription for a GLP-1a. Within this cohort, treatment was defined as having ≥2 GLP-1a prescriptions at a therapeutic dosage separated by ≥10 months. The cohort included 693 patients of whom 393 (57%) were treated with GLP-1a therapy. The treatment group had a mean change in body mass index (BMI) of -0.83 kg/m² (±2.88) compared to -0.70 kg/m² (±2.99) in the without GLP-1a group (p = 0.57). Treated patients had a mean change in HbA1c of -1.00% (±2.07) compared to -0.83% (±1.92) in the without GLP-1a group (p = 0.27). For treated and without GLP-1a patients, respectively, the proportion of patients with a decrease in BMI was 65 versus 64% (p = 0.86), and the proportion with a decrease in HbA1c was 73 versus 69% (p = 0.28). In clinical practice, GLP-1a therapy was associated with more modest reductions in weight and HbA1c than shown in prior RCTs. As GLP-1a use continues to expand throughout primary care, the real-world impact of this pharmacotherapy will require further evaluation.

Previously, many studies have reported changes in the gut microbiota of patients with colorectal cancer (CRC). While CRC is a well-described disease, the relationship between its development and features of the intestinal microbiome is still being understood. Evidence linking Fusobacterium nucleatum enrichment in colorectal tumor tissue has prompted the elucidation of various molecular mechanisms and tumor-promoting attributes. In this review we highlight various aspects of our understanding of the relationship between the development of CRC and the alteration of intestinal microbiome, focusing specifically on the role of F. nucleatum. As the amount of F. nucleatum DNA in CRC tissue is associated with shorter survival, it may potentially serve as a prognostic biomarker, and most importantly may open the door for a role in CRC treatment.