Context: Ovarian cancer remains a significant global health concern, characterized by limited therapeutic options and high mortality rates, primarily due to late-stage diagnosis and resistance to conventional therapies. Antibody-drug conjugates (ADCs) represent a promising targeted therapeutic approach for this malignancy.
Evidence acquisition: A comprehensive literature search was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar databases. Studies were selected based on their relevance to the development of ADCs, as well as their preclinical and clinical evaluation in ovarian cancer, resistance mechanisms, and toxicity profiles.
Results: This review summarizes a range of ADCs targeting tumor-associated antigens in ovarian cancer, including mirvetuximab soravtansine (MIRV), trastuzumab deruxtecan (T-DXd), datopotamab deruxtecan (Dato-DXd), sacituzumab tirumotecan (SKB-264), PF-06664178, anetumab ravtansine (BAY 94-9343), BMS-986148, DMOT4039A, RC88, lifastuzumab vedotin (DNIB0600A), upifitamab rilsodotin (ABBV-181), ZW220, DMUC4064A, and sofituzumab vedotin (DMUC5754A). Resistance mechanisms, toxicity profiles, and the potential for combination therapies and next-generation ADC designs are also discussed.
Conclusions: The ADCs hold significant potential to reshape the treatment landscape for ovarian cancer by providing targeted therapeutic options. Further research is required to optimize patient selection, address resistance mechanisms, and improve safety profiles.
Context: Chronic kidney disease (CKD) is a significant global health issue, characterized by its progressive nature and the limited effectiveness of conventional treatments. Chinese herbal medicine (CHM) has been used for centuries in East Asia to manage CKD by targeting key pathological processes. This review focuses on synthesizing evidence from various studies to explore the potential role of CHM in managing CKD, particularly through classical formulations, individual herbs, and their bioactive compounds with known nephroprotective effects.
Evidence acquisition: The review synthesizes evidence from preclinical studies, randomized controlled trials (RCTs), and meta-analyses to assess the effectiveness of CHM in CKD management. It highlights the use of classical CHM formulations like Liuwei Dihuang decoction, Zhenwu decoction, Shen-Qi-Wan (SQW), and Yu-Quan Wan (YQW), which are based on CHM theory and syndrome differentiation. Additionally, individual herbs such as Astragalus membranaceus, Salvia miltiorrhiza, Rheum officinale, Tripterygium wilfordii Hook F (TwHF), and Cordyceps sinensis are discussed for their nephroprotective bioactive compounds that provide multi-targeted effects, including anti-inflammatory, anti-fibrotic, antioxidant, and immunomodulatory actions.
Results: Integration of CHM with standard therapy has shown promising results in improving renal function and reducing proteinuria, especially in patients with CKD and IgA nephropathy (IgAN). Evidence supports the multi-mechanistic actions of CHM, including the potential for its anti-inflammatory, anti-fibrotic, antioxidant, and immunomodulatory effects to positively impact CKD progression.
Conclusions: Despite the growing body of evidence supporting the therapeutic value of CHM in CKD management, challenges still exist, such as the standardization of herbal preparations, ensuring safety, and gaining regulatory approval. For CHM to be more broadly integrated into evidence-based nephrology practice, further high-quality clinical research and harmonization of regulatory frameworks will be crucial. Overall, CHM offers a complementary approach to CKD treatment that aligns with classical principles and multi-targeted actions, contributing to a broader global strategy for CKD management.
Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic hepatic condition that can progress to non-alcoholic steatohepatitis (NASH) through inflammatory processes.
Objectives: This research aimed to examine the impact of an aqueous extract of Capparis spinosa fruit and the lipid-lowering agent fenofibrate (FENO) on hepatic inflammation and steatosis in rats subjected to a high-fat emulsion.
Methods: Male Wistar rats were given a high-fat diet (HFD) to develop NASH. The high-fat treated rats were categorized into three groups and administered either C. spinosa, FENO, or a vehicle control. Histopathological analyses, Liver Index computation, and measurements of body and liver weights were conducted. Serum levels of liver enzymes, adiponectin, and leptin were also assessed. Additionally, the expression of hepatic genes for monocyte chemoattractant protein 1 (MCP-1), transforming growth factor-beta (TGF-β), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) was evaluated.
Results: The administration of C. spinosa extract to the NASH model rodents significantly increased their adiponectin levels while substantially decreasing their levels of leptin, alanine aminotransferase (ALT), and aspartate transaminase (AST). Hepatic steatosis, liver inflammation, and collagen deposition were significantly reduced by C. spinosa treatment. Furthermore, the hepatic mRNA expression of the proinflammatory cytokines TNF-α, IL-6, and MCP-1, as well as the hepatic fibrogenic marker TGF-β1, was significantly reduced by C. spinosa treatment. The FENO exhibited a comparable pattern of response.
Conclusions: Our findings suggest that C. spinosa has a positive anti-inflammatory effect and may protect the liver against hepatic fibrosis, inflammation, and steatosis. These findings demonstrate the promising therapeutic potential of C. spinosa in the management of NASH.
Background: Chronic fatigue syndrome (CFS) is a complex and debilitating disorder characterized by extreme fatigue that cannot be explained by any underlying medical condition. Chronic fatigue syndrome significantly impacts the daily lives of patients with chronic obstructive pulmonary disease (COPD). Currently, there is no definitive treatment for CFS.
Objectives: This study aimed to determine the effects of Crocus sativus L. herbal product on improving CFS and quality of life (QOL) in patients with COPD.
Methods: This study was conducted as a randomized, double-blind, placebo-controlled clinical trial. Chronic obstructive pulmonary disease patients with CFS were randomly assigned to either the intervention or control group using block randomization generated by the Sealed Envelope online tool. Data were coded to ensure that both researchers and analysts were blinded to group assignments. Participants in the intervention group (n = 37) received 30 mg of dry saffron extract capsules twice daily for eight weeks, while those in the control group (n = 34) received a placebo. The primary outcome was the effect of C. sativus on CFS, assessed using the Chronic Respiratory Questionnaire (CRQ) and the Manchester COPD Fatigue Scale (MCFS). The secondary outcome was the effect on QOL, measured using the St. George's Respiratory Questionnaire (SGRQ). Patients were evaluated at baseline, after one month, and after two months.
Results: Based on mixed repeated measures ANOVA models, the effect of C. sativus on CRQ total scores was significant (P < 0.001), while the effect on the Dyspnea subscale was not significant (P = 0.38). The effect on chronic fatigue status based on MCFS was significant (P < 0.001). The effect on total QOL score based on SGRQ was also significant (P = 0.012), while the effect on the Symptoms subscale was not significant (P = 0.158).
Conclusions: The findings indicate that C. sativus herbal product is effective in reducing CFS and improving QOL in COPD patients. However, it may not be effective in reducing COPD symptoms, including dyspnea.
Background: Neonatal hypoxic ischemia (HI) injury results in neuronal cell death, which remains clinically challenging to mitigate. Omega-3 polyunsaturated fatty acids (PUFAs) are known for their antioxidative and anti-inflammatory effects. Folic acid (FA) correlates with apoptosis in neural stem cells and neurons.
Objectives: This study aimed to evaluate whether combined PUFA and FA supplementation mitigates neonatal HI brain injury by reducing apoptosis, inflammation, neurotransmitter imbalance, and electrophysiological dysfunction, thereby offering enhanced neuroprotection and functional recovery.
Methods: Brain tissue damage, orthodromic population spike (OPS), and hypoxic injury potential (HIP) were measured. Amino acid neurotransmitter concentration in the hippocampus sections was measured. Markers of inflammation and apoptosis were assayed from HI-induced rat brains and lipopolysaccharide (LPS)-induced microglia BV-2 cells.
Results: The HI caused severe damage to brain tissues that were potentially prevented by PUFA-FA by reducing the infarct size by 88%. The PUFA-FA treatment decreased the latency time (51 and 43 s) and increased swimming velocity (152 and 170 mm/s) on training days 3 and 5. The PUFA-FA showed an improved OPS decay time of 327 s, OPS recovery rate (62 s), and recovery amplitude (58 s). Whereas it caused an average 57% HIP incidence with a notably delayed onset (564 s) and duration (182 s). The PUFA-FA treatment also decreased the HI-induced release of amino acid neurotransmitters (Asp, Glu, and Gly) and GABA. The PUFA-FA suppressed the levels of proinflammatory cytokines and chemokines (iNOS, COX-2, TNF-α, IL-1β, and IL-6) and might mediate the inhibition of the NF-κB signaling pathway. The PUFA-FA reduced apoptosis as evidenced by lowered expression of AIF, caspase-3, and PARP genes.
Conclusions: The PUFA and FA reduced HI-induced brain infarct size, with the combination showing greater protection compared to individual effects. Both improved cognitive performances, decreasing latency times and enhancing swimming velocity. The PUFA-FA supplementation synergistically restored memory, learning, and motor functions, highlighting strong neuroprotective effects against HI-induced neuronal degeneration and cognitive impairments.
Background: The cross-talk between mesenchymal-epithelial transition factor (c-MET) and epidermal growth factor receptor (EGFR) plays a role in breast cancer (BC) progression and resistance to various targeted therapies. Consequently, the simultaneous overexpression of c-MET and EGFR in triple-negative breast cancer (TNBC) is associated with poorer clinicopathological outcomes and increased risks. Despite the development of new c-MET and EGFR inhibitors, the high cost of these drugs makes them inaccessible to most patients.
Objectives: Our study investigated the therapeutic potential of existing drugs by repurposing small molecules against these two receptors.
Methods: A database of 2028 small molecule agents was screened using pharmacophore-based virtual screening protocols. To rank the compounds, Gibbs free binding energies were used to analyze their binding energies and interactions with these two receptors.
Results: It was determined that ARR-4 and ADHHRRR-1 represented the most validated pharmacophore models for c-MET and EGFR, respectively, using receiver operating characteristic (ROC), enrichment factor (EF)1%, and Boltzmann-enhanced discrimination of receiver operating characteristic (BEDROC) scores. As a result, eight small molecules were proposed as potential dual inhibitors of c-MET and EGFR, with pasireotide showing the highest affinity for both. According to our analysis of molecular dynamic simulations, pasireotide, the most energetically favorable compound, is proposed as a dual inhibitor of c-MET and EGFR.
Conclusions: Considering pasireotide's potential to target c-MET and EGFR pathways, our findings provide a strong rationale for its further preclinical validation in the treatment of TNBC. The demonstrated efficacy and safety of pasireotide in this aggressive subtype of cancer can now be evaluated through subsequent studies.
Background: Doxorubicin, one of the most widely used chemotherapy drugs, has several side effects, including cardiotoxicity.
Objectives: We investigated the effect of melatonin on doxorubicin-induced cardiotoxicity in breast cancer patients treated with a regimen of doxorubicin plus cyclophosphamide (AC).
Methods: This is a triple-blind, placebo-controlled, randomized clinical trial conducted at the Cancer Institute of Imam Khomeini Hospital, Tehran University of Medical Sciences. Using the block randomization method, 63 breast cancer patients participated in the study and were randomly divided into two groups of 32 and 31, receiving melatonin (10 mg) and a placebo, respectively. The chemotherapy regimen for these patients included doxorubicin 60 mg/m2. Melatonin or placebo was started concurrently with doxorubicin at bedtime in the first cycle of chemotherapy and continued until one week after the end of the last cycle of chemotherapy. Echocardiography was performed before initiation and one week after the last chemotherapy session. Also, the cardiac troponin I (cTnI) and creatine kinase-myoglobin binding (CK-MB) levels were measured upon study recruitment, one week after the second and fourth chemotherapy sessions.
Results: The echocardiography showed that after the intervention, the left ventricular ejection fraction (LVEF) was higher in the melatonin group than in the placebo group, but it was insignificant. Meanwhile, the average global longitudinal strain (GLS) was significantly higher in the melatonin group than in the placebo group at the end of the study. The cTnI and CK-MB biomarker levels were lower in the melatonin group compared to the placebo group. These changes were significant for cTnI but not for CK-MB.
Conclusions: Melatonin may be effective in the prevention of doxorubicin-induced cardiotoxicity based on the improvement in GLS and biomarker levels.
Context: Intestinal fibrosis, a severe complication of Crohn's disease (CD), arises from multifactorial interactions, including chronic inflammation, genetic predisposition, gut microbiota dysbiosis, and impaired mucosal barrier function.
Objectives: Since intestinal fibrosis often leads to irreversible stenosis and obstruction symptoms, this article will focus on a series of reviews on the progress of traditional Chinese and Western medicine in the diagnosis and treatment of intestinal fibrosis in CD.
Methods: We conducted a systematic literature search in PubMed, CNKI, and Wanfang databases using the keywords: 'Crohn's disease', 'intestinal fibrosis', and 'Traditional Chinese Medicine (TCM)'. The initial search yielded 216 articles. After removing duplicates (n = 146), 70 articles underwent full-text screening based on predefined criteria.
Results: Current diagnostic modalities for CD-related intestinal fibrosis are well-established. However, neither pharmacological agents nor TCM therapies have demonstrated definitive efficacy in reversing fibrosis in clinical settings.
Conclusions: Despite the current absence of clinically approved antifibrotic drugs, this review synthesizes critical advances in mechanistic understanding and emerging therapeutic strategies. We highlight the urgent unmet clinical need and propose integrative medicine as a promising paradigm shift for fibrosis management. While no therapies yet fully reverse established fibrosis, this review provides three key contributions: Systematically maps molecular pathways from inflammation to fibrosis, identifies knowledge gaps in TCM translational research, and proposes a "control-prevent-reverse" framework for future drug development. These insights are timely given the rising CD prevalence in China and increasing NIH funding for antifibrotic research.
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