Exploring the Effects and Potential Mechanisms of Hesperidin for the Treatment of CPT-11-Induced Diarrhea: Network Pharmacology, Molecular Docking, and Experimental Validation.

Chemotherapy-induced diarrhea (CID) is a potentially serious side effect that often occurs during anticancer therapy and is caused by the toxic effects of chemotherapeutic drugs on the gastrointestinal tract, resulting in increased frequency of bowel movements and fluid contents. Among these agents, irinotecan (CPT-11) is most commonly associated with CID. Hesperidin (HPD), a flavonoid glycoside found predominantly in citrus fruits, has anti-oxidation properties and anti-inflammation properties that may benefit CID management. Nevertheless, its potential mechanism is still uncertain. In this study, we firstly evaluated the pharmacodynamics of HPD for the treatment of CID in a mouse model, then used network pharmacology and molecular docking methods to excavate the mechanism of HPD in relieving CID, and finally further proved the predicted mechanism through molecular biology experiments. The results demonstrate that HPD significantly alleviated diarrhea, weight loss, colonic pathological damage, oxidative stress, and inflammation in CID mice. In addition, 74 potential targets for HPD intervention in CID were verified by network pharmacology, with the top 10 key targets being AKT1, CASP3, ALB, EGFR, HSP90AA1, MMP9, ESR1, ANXA5, PPARG, and IGF1. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the PI3K-Akt pathway, FoxO pathway, MAPK pathway, TNF pathway, and Ras pathway were most relevant to the HPD potential treatment of CID genes. The molecular docking results showed that HPD had good binding to seven apoptosis-related targets, including AKT1, ANXA5, CASP3, HSP90AA1, IGF1, MMP9, and PPARG. Moreover, we verified apoptosis by TdT-mediated dUTP nick-end labeling (TUNEL) staining and immunohistochemistry, and the hypothesis about the proteins above was further verified by Western blotting in vivo experiments. Overall, this study elucidates the potential and underlying mechanisms of HPD in alleviating CID.

The efficacy of Salvia-ligustrazine and Ligustrazine in treating gestational hypertension: A systematic review and meta-analysis.

Pregnancy-induced hypertension syndrome (PIH), a prevalent and critical condition, has garnered increasing attention due to its significant impact on maternal and fetal health outcomes. The conventional treatment approaches rely on magnesium sulfate and various antihypertensive drugs; however, the clinical efficacy of these treatments is limited, highlighting the need to explore alternative avenues for improvement. Recently, a growing number of clinical studies have investigated the use of Salvia-ligustrazine or Ligustrazine in combination with conventional therapy. A comprehensive synthesis and critical analysis of these studies is necessary to evaluate the efficacy and safety of Salvia-ligustrazine or Ligustrazine in treating PIH. We sought all articles published prior to December 2, 2023, from seven databases to identify randomized controlled trials (RCTs) that involved traditional Chinese medicine Salvia-ligustrazine or Ligustrazine in combination with Western medicines for the conventional treatment of PIH, according to predefined inclusion criteria. The studies were assessed using the Cochrane Risk of Bias tool (ROB2.0), and meta-analyses were conducted using Stata 15.0 statistical software. We analyzed 47 RCTs encompassing 4,517 patients. The results demonstrated that combining Salvia-ligustrazine or Ligustrazine with Western medications was more efficacious than using Western medications alone. This combination improved the overall response rate, reduced the incidence of adverse pregnancy outcomes for mothers and infants, and decreased the occurrence of side effects associated with PIH treatment. While we evaluated the efficacy of traditional Chinese medicine injections of Salvia-ligustrazine or Ligustrazine alongside conventional Western treatments, our conclusions must be considered provisional due to potential bias and the limited availability of RCTs.

Clinical Characteristics and Outcome Between Gallbladder Squamous Cell Carcinoma and Adenocarcinoma: A Propensity Matched Analysis Based on the Surveillance, Epidemiology, and End Results Database.

Background: Gallbladder squamous cell carcinoma (GSCC) is a rare carcinoma with limited evidence in literature, making it particularly difficult to study. Surveillance, Epidemiology, and End Results Database (SEER) were used to stress the clinicopathological features and outcomes associated with this tumor. Methods: SEER registries were used to identify GSCC and gallbladder adenocarcinoma (GAC) cases from 2004 to 2015. The Propensity matching (PSM) method was used for minimized potential difference between the two types and the utmost. Patients with GSCC versus GAC were compared using the clinicopathological features and outcomes. Results: There were 121 patients with GSCC and 6 580 patients had GAC. Compared with the GAC cohort, the GSCC cohort had a lower proportion of well-differentiated histology (3.3% vs. 12.1%, p < 0.001) and was diagnosed at a later T-stage (p < 0.001). Regarding treatment, patients treated with surgery, chemotherapy or radiation were associated with significantly better outcome than patients without undergoing these treatment modalities. In both univariate and multivariate analyses, GSCC histology was associated with worse prognosis than GAC histology. Conclusions: Patients with GSCC were associated with a worse outcome than the GAC cohort. The independent risk factors for patients with GSCC are surgery and chemotherapy.

Rare capecitabine-induced acute hypertriglyceridemia with angina: a case report and review of the literature.

Capecitabine (CAP) is widely used to treat gastrointestinal and breast cancer, and is generally well tolerated. Hand-foot syndrome and gastrointestinal intolerance are the most common adverse effects. Capecitabine-induced hypertriglyceridemia (CIHT) is a very rare adverse effect and, from the reported literatures, is often neglected in clinical practice. Here, we report a case of CIHT with angina. A 58-year-old man with metastatic rectal cancer was admitted to the emergency room (ER) due to severe chest pain after treatment with CAP (Xeloda). The blood sample showed separation of blood and lipids, and the lipid profile revealed rapidly increased triglyceride and cholesterol levels. After fenofibrate therapy was administered, the patient's symptoms were relieved, and the repeat lipid test was normalized. Other causes of hyperlipidemia were carefully excluded, considering that the severe adverse effects of CAP had since abated. The earliest onset of the incidence as far as we know, the symptom of angina at the same time with CIHT, and distinct blood-lipid layer in blood sample all suggest the rarity of this case. We also concluded reports of CIHT and found that CIHT accidence was higher than our known. We genuinely hope that this case could awaken clinicians' awareness of the use of CAP.

Case Report: Immune and Genomic Characteristics Associated With Hyperprogression in a Patient With Metastatic Deficient Mismatch Repair Gastrointestinal Cancer Treated With Anti-PD-1 Antibody.

Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status of tumors is a distinct predictive biomarker of immune checkpoint inhibitors (ICIs) for colorectal and non-colorectal cancer populations. The overall response rate (ORR) varies from approximately 40% to 60%, indicating that nearly half of MSI-H tumors do not respond to ICIs. The mechanism of response heterogeneity in MSI-H/dMMR cancers is unclear. Some patients who have been treated with ICIs have developed a novel pattern of progression called hyperprogression, which is defined as unexpected accelerated tumor growth. No case of MSI-H/dMMR immunotherapy-associated hyperprogression has been reported in the literature. Here, we present the case of a patient with dMMR gastrointestinal cancer who suffered hyperprogressive disease (HPD) after treatment with nivolumab. We explored the potential mechanisms of HPD by clinical, immune, and genomic characteristics. Extremely high levels of serum LDH, low TMB and TILs, and the disruption of TGFß signaling, may be related to hyperprogression.

Intra-Abdominal Desmoplastic Small Round Cell Tumor: Current Treatment Options and Perspectives.

Intra-abdominal desmoplastic small round cell tumor (IDSRCT) is a rare and highly malignant soft tissue neoplasm, which is characterized by rapid progression and poor prognosis. The mechanism underlying the development of this neoplasm remains elusive, but all cases are characterized by the chromosomal translocation t (11;22) (p13; q12), which results in a formation of EWSR1-WT1 gene fusion. The diagnosis of IDSRCT is often made with core-needle tissue biopsy specimens or laparoscopy or laparotomy. Immunohistochemical analyses have shown the co-expression of epithelial, neuronal, myogenic, and mesenchymal differentiation markers. FISH or reverse transcription polymerase chain reaction detecting EWS-WT1 fusion can be performed to assist in molecular confirmation. There is no standard of care for patients with IDSRCT currently, and majority of newly diagnosed patients received the aggressive therapy, which includes >90% resection of surgical debulking, high-dose alkylator-based chemotherapy, and radiotherapy. More recently, targeted therapy has been increasingly administered to recurrent IDSRCT patients and has been associated with improved survival in clinical conditions. Immunotherapy as a possible therapeutic strategy is being explored in patients with IDSRCT. In this review, we summarize currently available knowledge regarding the epidemiology, potential mechanisms, clinical manifestations, diagnosis, treatment, and prognosis of IDSRCT to assist oncologists in comprehensively recognizing and accurately treating this malignancy.

Using Network Pharmacology and Molecular Docking to Explore the Mechanism of Shan Ci Gu (Cremastra appendiculata) Against Non-Small Cell Lung Cancer.

Background: In recent years, the incidence and mortality rates of non-small cell lung cancer (NSCLC) have increased significantly. Shan Ci Gu is commonly used as an anticancer drug in traditional Chinese medicine; however, its specific mechanism against NSCLC has not yet been elucidated. Here, the mechanism was clarified through network pharmacology and molecular docking. Methods: The Traditional Chinese Medicine Systems Pharmacology database was searched for the active ingredients of Shan Ci Gu, and the relevant targets in the Swiss Target Prediction database were obtained according to the structure of the active ingredients. GeneCards were searched for NSCLC-related disease targets. We obtained the cross-target using VENNY to obtain the core targets. The core targets were imported into the Search Tool for the Retrieval of Interacting Genes/Proteins database, and Cytoscape software was used to operate a mesh chart. R software was used to analyze the Gene Ontology biological processes (BPs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The core targets and active compounds were molecularly docked through Auto-Dock Vina software to predict the detailed molecular mechanism of Shan Ci Gu for NSCLC treatment. We did a simple survival analysis with hub gene to assess the prognosis of NSCLC patients. Results: Three compounds were screened to obtain 143 target genes and 1,226 targets related to NSCLC, of which 56 genes were related to NSCLC treatment. Shan Ci Gu treatment for NSCLC involved many BPs and acted on main targets including epidermal growth factor receptor (EGFR), ESR1, and SRC through signaling pathways including the endocrine resistance, EGFR tyrosine kinase inhibitor resistance, and ErbB signaling pathways. Shan Ci Gu might be beneficial for treating NSCLC by inhibiting cell proliferation and migration. Molecular docking revealed that the active compounds ß-sitosterol, stigmasterol, and 2-methoxy-9,10-dihydrophenanthrene-4,5-diol had good affinity with the core target genes (EGFR, SRC, and ESR1). Core targets included EGFR, SRC, ESR1, ERBB2, MTOR, MCL1, matrix metalloproteinase 2 (MMP2), MMP9, KDR, and JAK2. Key KEGG pathways included endocrine resistance, EGFR tyrosine kinase inhibitor resistance, ErbB signaling, PI3K-Akt signaling, and Rap1 signaling pathways. These core targets and pathways have an inhibitory effect on the proliferation of NSCLC cells. Conclusion: Shan Ci Gu can treat NSCLC through a multi-target, multi-pathway molecular mechanism and effectively improve NSCLC prognosis. This study could serve as a reference for further mechanistic research on wider application of Shan Ci Gu for NSCLC treatment.

Gallbladder carcinosarcoma: current perspectives and new development.

Introduction: Gallbladder carcinosarcoma (GBCS) is a rare neoplasm, and previous studies regarding to GBCS were case reports/case series, absence of large retrospective analyses, or systemic review. This review summarizes the current literature on accurate information of GBCS to assist clinicians to accurately diagnose and treat this malignancy.Areas covered: The authors retrieved relevant documents of GBCS from PubMed and Medline. This review elaborates on the knowledge of GBCS covering epidemiology, potential mechanism, clinical manifestation, diagnosis, treatment, and prognosis.Expert opinion: The majority of GBCS patients are easily misdiagnosed as GBC and usually treated as GBC. However, the biological behavior and outcome of GBCS is different from that of GBC. GBCS should be considered as a separate disease.

Cervical Carcinosarcoma: Current Understanding on Pathogenesis, Diagnosis, Management and Future Perspectives.

Cervical carcinosarcoma (CCS) is a rare aggressive tumor which was referred to as a sarcoma initially with its morbidity less than 1% of all cervical cancers. Four theories have been proposed for the pathogenesis of CCS. The "metaplastic theory," also called "monoclonal theory," has been widely accepted so far. The most common clinical symptom of CCS is abnormal vaginal bleeding. CCS is much less common than the counterparts in uterine corpus and usually confused with uterine carcinosarcoma (UCS) or common cervical cancer. The management for CCS has been mainly extrapolated from studies of UCS or cervical cancers. However, CCS has its special anatomical position and biological behaviors and is usually diagnosed at an early stage than UCS. Currently, there is no consensus on the survival, management and prognosis factors of CCS. We reviewed and summarized the literatures regarding to the epidemiology, clinical presentations, pathogenesis, diagnosis and treatment of CCS for providing clinicians with comprehensive information to diagnose and treat this malignancy.