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Journal of Cancer 2024Temozolomide is an imidazotetrazine with a long history in oncology especially for the high grade malignant glioma and metastatic melanoma. However, last year's new... (Review)
Review
Temozolomide is an imidazotetrazine with a long history in oncology especially for the high grade malignant glioma and metastatic melanoma. However, last year's new indications for its use are added. Its optimum pharmacodynamic profile, its ability to penetrate the blood-brain barrier, the existence of methylation of MGMT in solid tumors which enhances its efficacy, the identification of new agents that can overcome temozolomide's resistance, the promising role of temozolomide in turning immune cold tumors to hot ones, are leading to expand its use in other solid tumors, giving oncologists an additional tool for the treatment of advanced and aggressive neoplasms.
PubMed: 38817857
DOI: 10.7150/jca.94109 -
Outpatient management of obscure gastrointestinal bleeding: A new perspective in high-risk patients.World Journal of Gastroenterology May 2024Mid-gastrointestinal bleeding accounts for approximately 5%-10% of all gastrointestinal bleeding cases, and vascular lesions represent the most frequent cause. The...
Mid-gastrointestinal bleeding accounts for approximately 5%-10% of all gastrointestinal bleeding cases, and vascular lesions represent the most frequent cause. The rebleeding rate for these lesions is quite high (about 42%). We hereby recommend that scheduled outpatient management of these patients could reduce the risk of rebleeding episodes.
Topics: Humans; Gastrointestinal Hemorrhage; Ambulatory Care; Recurrence; Risk Factors; Treatment Outcome; Endoscopy, Gastrointestinal
PubMed: 38817662
DOI: 10.3748/wjg.v30.i19.2502 -
World Journal of Gastroenterology May 2024The gut microbiota is strongly associated with radiation-induced gut damage. This study aimed to assess the effectiveness and safety of intestinal microecological...
BACKGROUND
The gut microbiota is strongly associated with radiation-induced gut damage. This study aimed to assess the effectiveness and safety of intestinal microecological transplantation for treating patients with chronic radiation enteritis.
CASE SUMMARY
A 64-year-old female with cervical cancer developed abdominal pain, diarrhea, and blood in the stool 1 year after radiotherapy. An electronic colonoscopy was performed to diagnose chronic radiation enteritis. Two courses of intestinal microecological transplantation and full-length 16S rRNA microbiological analysis were performed. The patient experienced short- and long-term relief from symptoms without adverse effects. Whole 16S rRNA sequencing revealed significant differences in the intestinal flora's composition between patient and healthy donors. Pathogenic bacteria, such as and , were more in the patient. Beneficial bacteria such as , , , and were more in the healthy donors. Intestinal microbiota transplantation resulted in a significant change in the patient's intestinal flora composition. The composition converged with the donor's flora, with an increase in core beneficial intestinal bacteria, such as , and a decrease in pathogenic bacteria. Changes in the intestinal flora corresponded with the patients' alleviating clinical symptoms.
CONCLUSION
Intestinal microecological transplantation is an effective treatment for relieving the clinical symptoms of chronic radiation enteritis by altering the composition of the intestinal flora. This study provides a new approach for treating patients with chronic radiation enteritis.
Topics: Humans; Female; Middle Aged; Enteritis; Radiation Injuries; Gastrointestinal Microbiome; Fecal Microbiota Transplantation; Uterine Cervical Neoplasms; RNA, Ribosomal, 16S; Treatment Outcome; Chronic Disease; Colonoscopy; Intestines; Feces; Radiotherapy
PubMed: 38817661
DOI: 10.3748/wjg.v30.i19.2603 -
World Journal of Gastroenterology May 2024Variceal bleed represents an important complication of cirrhosis, with its presence reflecting the severity of liver disease. Gastric varices, though less frequently...
Variceal bleed represents an important complication of cirrhosis, with its presence reflecting the severity of liver disease. Gastric varices, though less frequently seen than esophageal varices, present a distinct clinical challenge due to its higher intensity of bleeding and associated mortality. Based upon the Sarin classification, GOV1 is the most common subtype of gastric varices seen in clinical practice.
Topics: Esophageal and Gastric Varices; Humans; Gastrointestinal Hemorrhage; Liver Cirrhosis; Treatment Outcome; Severity of Illness Index
PubMed: 38817659
DOI: 10.3748/wjg.v30.i19.2615 -
World Journal of Gastroenterology May 2024Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis (AP) but can be detected in various other diseases associated with lipase leakage... (Observational Study)
Observational Study
BACKGROUND
Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis (AP) but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surrounding the pancreas or reduced renal clearance and/or hepatic metabolism. This non-pancreatic hyperlipasemia (NPHL) is puzzling for attending physicians during the diagnostic procedure for AP. It would be clinically beneficial to identify the clinical and laboratory variables that hinder the accuracy of lipase diagnosis with the aim of improve it. A more precise description of the NPHL condition could potentially provide prognostic factors for adverse outcomes which is currently lacking.
AIM
To perform a detailed clinical and laboratory characterization of NPHL in a large prospective patient cohort with an assessment of parameters determining disease outcomes.
METHODS
A Hungarian patient cohort with serum lipase levels at least three times higher than the upper limit of normal (ULN) was prospectively evaluated over 31 months. Patients were identified using daily electronic laboratory reports developed to support an ongoing observational, multicenter, prospective cohort study called the EASY trial (ISRCTN10525246) to establish a simple, easy, and accurate clinical scoring system for early prognostication of AP. Diagnosis of NPHL was established based on ≥ 3 × ULN serum lipase level in the absence of abdominal pain or abdominal imaging results characteristic of pancreatitis.
RESULTS
A total of 808 patients [male, = 420 (52%); median age (IQR): 65 (51-75) years] were diagnosed with ≥ 3 × ULN serum lipase levels. A total of 392 patients had AP, whereas 401 had NPHL with more than 20 different etiologies. Sepsis and acute kidney injury (AKI) were the most prevalent etiologies of NPHL (27.7% and 33.2%, respectively). The best discriminative cut-off value for lipase was ≥ 666 U/L (sensitivity, 71.4%; specificity, 88.8%). The presence of AKI or sepsis negatively affected the diagnostic performance of lipase. NPHL was associated with a higher in-hospital mortality than AP (22.4% 5.1%, < 0.001). In multivariate binary logistic regression, not lipase but increased amylase level (> 244 U/L) and neutrophil-to-lymphocyte ratio (NLR) (> 10.37, OR: 3.71, 95%CI: 2.006-6.863, < 0.001), decreased albumin level, age, and presence of sepsis were independent risk factors for in-hospital mortality in NPHL.
CONCLUSION
NPHL is a common cause of lipase elevation and is associated with high mortality rates. Increased NLR value was associated with the highest mortality risk. The presence of sepsis/AKI significantly deteriorates the serological differentiation of AP from NPHL.
Topics: Humans; Lipase; Male; Female; Middle Aged; Prospective Studies; Pancreatitis; Aged; Prognosis; Hungary; Biomarkers; Adult
PubMed: 38817657
DOI: 10.3748/wjg.v30.i19.2538 -
World Journal of Gastroenterology May 2024Chronic enteropathy associated with the gene (CEAS) is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic... (Review)
Review
Chronic enteropathy associated with the gene (CEAS) is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss. This review explores the potential mechanisms underlying the pathogenesis of CEAS, focusing on the role of -encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2 (PGE2) levels. Studies have suggested that elevated PGE2 levels contribute to mucosal damage, inflammation, and disruption of the intestinal barrier. The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality, as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS. Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel, targeted therapies.
Topics: Humans; Organic Anion Transporters; Intestinal Mucosa; Chronic Disease; Dinoprostone; Intestine, Small; Anti-Inflammatory Agents, Non-Steroidal; Intestinal Diseases; Animals; Gastrointestinal Hemorrhage; Ulcer
PubMed: 38817656
DOI: 10.3748/wjg.v30.i19.2505 -
World Journal of Cardiology May 2024The use of anticoagulation therapy could prove to be controversial when trying to balance ischemic stroke and intracranial bleeding risks in patients with concurrent... (Review)
Review
The use of anticoagulation therapy could prove to be controversial when trying to balance ischemic stroke and intracranial bleeding risks in patients with concurrent cerebral amyloid angiopathy (CAA) and atrial fibrillation (AF). In fact, CAA is an age-related cerebral vasculopathy that predisposes patients to intracerebral hemorrhage. Nevertheless, many AF patients require oral systemic dose-adjusted warfarin, direct oral anticoagulants (such as factor Xa inhibitors) or direct thrombin inhibitors to control often associated with cardioembolic stroke risk. The prevalence of both CAA and AF is expected to rise, due to the aging of the population. This clinical dilemma is becoming increasingly common. In patients with coexisting AF and CAA, the risks/benefits profile of anticoagulant therapy must be assessed for each patient individually due to the lack of a clear-cut consensus with regard to its risks in scientific literature. This review aims to provide an overview of the management of patients with concomitant AF and CAA and proposes the implementation of a risk-based decision-making algorithm.
PubMed: 38817646
DOI: 10.4330/wjc.v16.i5.231 -
World Journal of Stem Cells May 2024Acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality rates. The use of pluripotent stem cells holds great promise for the treatment...
BACKGROUND
Acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality rates. The use of pluripotent stem cells holds great promise for the treatment of AKI. Urine-derived stem cells (USCs) are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive, simple, and low-cost approach and are induced with high multidifferentiation potential. Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined.
AIM
To investigate whether USCs can serve as a potential stem cell source to improve renal function and histological structure after experimental AKI.
METHODS
Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid. AKI severe combined immune deficiency (SCID) mice models were induced by means of an intramuscular injection with glycerol. USCs isolated from human-voided urine were administered tail veins. The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine. The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining. Meanwhile, we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells (MSCs).
RESULTS
Treatment with USCs significantly alleviated histological destruction and functional decline. The renal function was rapidly restored after intravenous injection of 5 × 10 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline. Results from secretion assays conducted demonstrated that both stem cell varieties released a wide array of cytokines and growth factors. This suggests that a mixture of various mediators closely interacts with their biochemical functions. Two types of stem cells showed enhanced tubular cell proliferation and decreased tubular cell apoptosis, although USC treatment was not more effective than MSC treatment. We found that USC therapy significantly improved renal function and histological damage, inhibited inflammation and apoptosis processes in the kidney, and promoted tubular epithelial proliferation.
CONCLUSION
Our study demonstrated the potential of USCs for the treatment of AKI, representing a new clinical therapeutic strategy.
PubMed: 38817335
DOI: 10.4252/wjsc.v16.i5.525 -
World Journal of Stem Cells May 2024Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size...
BACKGROUND
Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5'-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of . However, the positive regulators of are still unknown.
AIM
To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on transcription.
METHODS
Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for . Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on . Moreover, using the GENT2 platform, we analyzed the relationship between expression and overall survival in cancer patients.
RESULTS
In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for . Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate . Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5'-UTR of and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of . In addition, we discovered that high expression is always related to a more favorable prognosis in breast and lung cancer patients.
CONCLUSION
We first discovered that the transcription factor GATA2 plays a positive role in transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers.
PubMed: 38817334
DOI: 10.4252/wjsc.v16.i5.538 -
World Journal of Stem Cells May 2024Human induced pluripotent stem cell (hiPSC) technology is a valuable tool for generating patient-specific stem cells, facilitating disease modeling, and investigating...
BACKGROUND
Human induced pluripotent stem cell (hiPSC) technology is a valuable tool for generating patient-specific stem cells, facilitating disease modeling, and investigating disease mechanisms. However, iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics.
AIM
To investigate the impact of mutations on hiPSCs and determine whether hiPSC-derived extracellular vesicles (EVs) influence anomalous cell junction and differentiation potential.
METHODS
We employed a non-integrating reprogramming technique to generate peripheral blood-derived hiPSCs with and hiPSCs without a mutation. Chromosomal karyotype analysis, flow cytometry, and immunofluorescent staining were utilized for hiPSC identification. Transcriptomics and proteomics were employed to elucidate the expression patterns associated with cell junction abnormalities and cellular differentiation potential. Additionally, EVs were isolated from the supernatant, and their RNA and protein cargos were examined to investigate the involvement of hiPSC-derived EVs in stem cell junction and differentiation.
RESULTS
The generated hiPSCs, both with and without a mutation, exhibited normal karyotype and expressed pluripotency markers; however, hiPSCs with a mutation demonstrated anomalous adhesion capability and differentiation potential, as confirmed by transcriptomic and proteomic profiling. Furthermore, hiPSC-derived EVs were involved in various biological processes, including cell junction and differentiation.
CONCLUSION
HiPSCs with a mutation displayed altered junction characteristics and aberrant differentiation potential. Furthermore, hiPSC-derived EVs played a regulatory role in various biological processes, including cell junction and differentiation.
PubMed: 38817331
DOI: 10.4252/wjsc.v16.i5.512