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Ecotoxicology and Environmental Safety Oct 2023Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry....
Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry. The critical issue that needs to be solved urgently is to evaluate the safety of traditional Chinese medicine systematically and effectively. Podophyllotoxin (PPT) is a highly active compound extracted from plants of the genus Podophyllum such as Dysosma versipellis (DV). However, its high toxicity and toxicity to multiple target organs affect the clinical application, such as the liver and kidney. Based on the concurrent effects of PPT's medicinal activity and toxicity, it would be a good example to conduct a systematic review of its safety. Therefore, this study revolves around the Toxicological Evidence Chain (TEC) concept. Based on PPT as the main toxic constituent in DV, observe the objective toxicity impairment phenotype of animals. Evaluate the serum biochemical indicators and pathological tissue sections for substantial toxic damage results. Using metabolomics, lipidomics, and network toxicology to evaluate the nephrotoxicity of PPT from multiple perspectives systematically. The results showed that PPT-induced nephrotoxicity manifested as renal tubular damage, mainly affecting metabolic pathways such as glycerophospholipid metabolism and sphingolipid metabolism. PPT inhibits the autophagy process of kidney cells through the PI3K/Akt/mTOR and Nrf2/HO1 pathways and induces the activation of oxidative stress in the body, thereby causing nephrotoxic injury. This study fully verified the feasibility of the TEC concept for the safety and toxicity evaluation of traditional Chinese medicine. Provide a research template for systematically evaluating the safety of traditional Chinese medicine.
Topics: Animals; Rats; Kidney; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases; Podophyllotoxin; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases; Podophyllum; Drugs, Chinese Herbal
PubMed: 37651795
DOI: 10.1016/j.ecoenv.2023.115392 -
Journal of Orthopaedic Surgery and... Mar 2024Many KOA patients have not reached indications for surgery, thus we need to find effective non-surgical treatments. Acupuncture is thought to have the potential to... (Meta-Analysis)
Meta-Analysis
Efficacy and immune-inflammatory mechanism of acupuncture-related therapy in animal models of knee osteoarthritis: a preclinical systematic review and network meta-analysis.
BACKGROUND
Many KOA patients have not reached indications for surgery, thus we need to find effective non-surgical treatments. Acupuncture is thought to have the potential to modulate inflammation and cytokines in KOA through the immune system. However, the mechanisms have not been elucidated, and there is no network Meta-analysis of acupuncture on KOA animals. So we evaluate the effect and mechanism of acupuncture-related therapy in KOA animals.
METHODS
A comprehensive search was conducted in multiple databases including PubMed, Web of Science, Embase, CBM, CNKI, WanFang, and VIP Database to identify relevant animal studies focusing on acupuncture therapy for KOA. The included studies were assessed for risk of bias using SYRCLE's Risk of Bias tool. Subsequently, pair-wise meta-analysis and network meta-analysis were performed using Stata 15.0 software, evaluating outcomes such as Lequesne index scale, Mankin score, IL-1β, TNF-α, MMP3, and MMP13.
RESULTS
56 RCTs with 2394 animals were included. Meta-analysis showed that among the 6 outcomes, there were significant differences between acupuncture and model group; the overall results of network meta-analysis showed that the normal group or sham operation group performed the best, followed by the acupotomy, acupuncture, and medicine group, and the model group had the worst effect, and there were significant differences between 6 interventions.
CONCLUSIONS
Acupuncture-related therapy can be a possible treatment for KOA. The mechanism involves many immune-inflammatory pathways, which may be mediated by DAMPs/TLR/NF-κB/MAPK,PI3K/Akt/NF-κB pathway, or IFN-γ/JAK-STAT pathway. It needs to be further confirmed by more high-quality animal experiments or meta-analysis.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO identifier: CRD42023377228.
Topics: Animals; Humans; Osteoarthritis, Knee; Network Meta-Analysis; Janus Kinases; NF-kappa B; Phosphatidylinositol 3-Kinases; STAT Transcription Factors; Signal Transduction; Acupuncture Therapy; Models, Animal
PubMed: 38459553
DOI: 10.1186/s13018-024-04660-9 -
Clinical Lymphoma, Myeloma & Leukemia Feb 2024No established standard of care exists for relapsed/refractory (RR) follicular lymphoma (FL) after ≥2 prior therapies. We conducted indirect treatment comparisons...
BACKGROUND
No established standard of care exists for relapsed/refractory (RR) follicular lymphoma (FL) after ≥2 prior therapies. We conducted indirect treatment comparisons (ITCs) to compare the efficacy and tolerability of mosunetuzumab with those of available treatments used in this setting.
METHODS
A systematic literature review (SLR) and subsequent feasibility assessments were conducted to identify the most suitable comparator studies in terms of design, available endpoints and populations. Imbalances in patient characteristics between NCT02500407 and studies featuring aggregate or patient-level data availability were accounted for using matching-adjusted indirect comparison (MAIC) and propensity score-based methodologies, respectively.
RESULTS
ZUMA-5, ELARA, DELTA, DYNAMO, UNITY-NHL, AUGMENT and NCT01897571 passed the MAIC feasibility assessment. Patient-level data were available from GADOLIN, CONTRALTO and NCT02257567. MAIC results generally favored mosunetuzumab over tazemetostat in EHZ2wild-type patients for all outcomes and over PI3K inhibitors for complete response (CR), objective response rate (ORR), discontinuations due to adverse events and progression-free survival (PFS) with umbralisib. MAICs favored CART therapies for PFS and, to a lesser extent, ORR and CR. Comparisons with anti-CD20 antibody-based regimens yielded mixed results.
CONCLUSIONS
ITCs suggest that mosunetuzumab may lead to superior outcomes over tazemetostat (in EHZ2wild-type patients) and PI3K inhibitors and may be a promising alternative to re-challenging with a different anti-CD20 regimen in patients who relapse after ≥2 prior anti-CD20 lines. Although preliminary results somewhat favored CART therapies, limitations and uncertainties remain because of intrinsic differences in study design. Mosunetuzumab could thus be a promising treatment option for patients with RR FL after ≥2 prior therapies.
Topics: Humans; Lymphoma, Follicular; Phosphatidylinositol 3-Kinases; Neoplasm Recurrence, Local; Antineoplastic Agents; Antibodies, Bispecific; Benzamides; Biphenyl Compounds; Morpholines; Pyridones
PubMed: 37981564
DOI: 10.1016/j.clml.2023.09.007 -
Frontiers in Endocrinology 2023Immune checkpoint inhibitor (ICI)- and phosphatidylinositol-3-kinase inhibitor (PI3Ki)-related diabetes mellitus are common side effects of anti-tumor drug use that...
Immune checkpoint inhibitor (ICI)- and phosphatidylinositol-3-kinase inhibitor (PI3Ki)-related diabetes mellitus are common side effects of anti-tumor drug use that present mainly as hyperglycemia. Here, we present two case reports of diabetes mellitus caused by the use of tremelimumab and apalutamide, respectively, in cancer treatment, and a comprehensive, comparative review of the literature on these forms of diabetes. Case 1 presented with diabetic ketoacidosis and was diagnosed with ICI-related diabetes mellitus and treated with insulin. Case 2 was diagnosed with PI3Ki-related diabetes mellitus, and her blood glucose level returned to normal with the use of metformin and dapagliflozin. We systematically searched the PubMed database for articles on ICI- and PI3Ki-related diabetes mellitus and characterized the differences in clinical features and treatment between these two forms of diabetes.
Topics: Female; Humans; Antineoplastic Agents; Diabetes Mellitus; Diabetic Ketoacidosis; Hyperglycemia; Immune Checkpoint Inhibitors; Phosphatidylinositols
PubMed: 37732122
DOI: 10.3389/fendo.2023.1236946 -
Systematic Reviews Apr 2024Breast cancer incidence has been on the rise significantly in the Asian population, occurring at an earlier age and a later stage. The potential predictive value of... (Meta-Analysis)
Meta-Analysis
Exploring the effectiveness of molecular subtypes, biomarkers, and genetic variations as first-line treatment predictors in Asian breast cancer patients: a systematic review and meta-analysis.
BACKGROUND
Breast cancer incidence has been on the rise significantly in the Asian population, occurring at an earlier age and a later stage. The potential predictive value of molecular subtypes, biomarkers, and genetic variations has not been deeply explored in the Asian population. This study evaluated the effect of molecular subtype classification and the presence or absence of biomarkers and genetic variations on pathological complete response (pCR) after neoadjuvant treatment in Asian breast cancer patients.
METHODS
A systematic search was conducted in MEDLINE (PubMed), Science Direct, Scopus, and Cochrane Library databases. Studies were selected if they included Asian breast cancer patients treated with neoadjuvant chemotherapy and contained data for qualitative or quantitative analyses. The quality of the included studies was assessed using the Newcastle Ottawa Scale. Following the random effects model, pooled odds ratios or hazard ratios with 95% confidence intervals for pCR were analysed using Review Manager Software. Heterogeneity between studies was assessed using Cochran's Q-test and I test statistics.
RESULTS
In total, 19,708 Asian breast cancer patients were pooled from 101 studies. In the neoadjuvant setting, taxane-anthracycline (TA) chemotherapy showed better pCR outcomes in triple-negative breast cancer (TNBC) (p<0.0001) and human epidermal growth factor receptor 2 enriched (HER2E) (p<0.0001) than luminal breast cancer patients. Similarly, taxane-platinum (TP) chemotherapy also showed better pCR outcomes in TNBC (p<0.0001) and HER2E (p<0.0001). Oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, HER2-positive and high Ki-67 were significantly associated with better pCR outcomes when treated with either TA or TP. Asian breast cancer patients harbouring wildtype PIK3CA were significantly associated with better pCR outcomes when treated with TA in the neoadjuvant setting (p=0.001).
CONCLUSIONS
In the neoadjuvant setting, molecular subtypes (HER2E and TNBC), biomarkers (ER, PR, HER2, HR, Ki-67, nm23-H1, CK5/6, and Tau), and gene (PIK3CA) are associated with increased pCR rates in Asian breast cancer patients. Hence, they could be further explored for their possible role in first-line treatment response, which can be utilised to treat breast cancer more efficiently in the Asian population. However, it needs to be further validated with additional powered studies.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021246295.
Topics: Female; Humans; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Class I Phosphatidylinositol 3-Kinases; Genetic Variation; Ki-67 Antigen; Receptor, ErbB-2; Receptors, Estrogen; Taxoids; Triple Negative Breast Neoplasms
PubMed: 38576013
DOI: 10.1186/s13643-024-02520-5 -
Frontiers in Nutrition 2024Studies have shown that sphingomyelin (SM) and its metabolites play signaling roles in the regulation of human health. Endogenous SM is involved in metabolic syndrome...
BACKGROUND
Studies have shown that sphingomyelin (SM) and its metabolites play signaling roles in the regulation of human health. Endogenous SM is involved in metabolic syndrome (MetS), while dietary SM supplementation may maintain lipid metabolism and prevent or alleviate MetS. Therefore, we hypothesized that dietary SM supplementation is beneficial for human health.
AIMS
In order to examine the impacts of dietary SM on metabolic indexes in adults without MetS, we performed a meta-analysis to test our hypothesis.
METHODS
A comprehensive search was performed to retrieve randomized controlled trials that were conducted between 2003 and 2023 to examine the effects of dietary SM supplementation on metabolic parameters in the Cochrane Library, PubMed, Web of Science, Embase, and ClinicalTrials.gov databases. RevMan 5.4 and Stata 14.0 software were used for meta-analysis, a sensitivity analysis, the risk of bias, and the overall quality of the resulted evidence.
RESULTS
Eventually, 10 articles were included in this meta-analysis. Dietary SM supplementation did not affect the endline blood SM level. When compared to the control, SM supplementation reduced the blood total cholesterol level [MD: -12.97, 95% CI: (-14.57, -11.38), < 0.00001], low-density lipoprotein cholesterol level [MD: -6.62, 95% CI: (-10.74, -2.49), = 0.002], and diastolic blood pressure [MD: -3.31; 95% CI (-4.03, -2.58), < 0.00001] in adults without MetS. The supplementation also increased high-density lipoprotein level [MD:1.41, 95% CI: (0.94, 1.88), < 0.00001] and muscle fiber conduction velocity [MD: 95% 1.21 CI (0.53, 1.88), = 0.0005]. The intake of SM had no effect on the blood phospholipids and lyso-phosphatidylcholine, but slightly decreased phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol concentrations. Dietary SM supplementation reduced insulin level [MD: -0.63; 95% CI (-0.96, -0.31), = 0.0001] and HOMA-IR [MD: -0.23; 95% CI (-0.31, -0.16), < 0.00001] without affecting blood levels of glucose and inflammatory cytokines.
CONCLUSION
Overall, dietary SM supplementation had a protective effect on blood lipid profiles and insulin level, but had limited impacts on other metabolic parameters in adults without MetS. More clinical trials and basic research are required.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42023438460.
PubMed: 38463938
DOI: 10.3389/fnut.2024.1363077 -
Current Cancer Drug Targets Jan 2024Phosphatidylinositol 3-kinase (PI3K) inhibitors belong to the class of drugs that inhibit the activity of the PI3K protein, which is commonly overexpressed in breast...
BACKGROUND
Phosphatidylinositol 3-kinase (PI3K) inhibitors belong to the class of drugs that inhibit the activity of the PI3K protein, which is commonly overexpressed in breast cancer cells. However, there is a need to summarize the evidence to provide conclusive advice on the benefit of PI3K inhibitors in breast cancer patients. Therefore, this review assessed the effectiveness and safety of the PI3K inhibitors amongst breast cancer patients.
METHODS
Searches were made in PubMed Central, EMBASE, MEDLINE, SCOPUS, CENTRAL, WHO trial registry and Clinicaltrials.gov up to December 2022. Meta-analysis was executed using the random-effects model. Pooled hazard ratio (HR)/risk ratio (RR) was reported with 95% confidence intervals (CIs).
RESULTS
In total, 13 studies were included in the analysis. Most were multi-country studies and had a higher risk of bias. Regarding the efficacy parameters, pooled HR for progression-free survival was 0.79 (95%CI: 0.67-0.92), pooled RR for complete response was 1.54 [95%CI: 1.14 to 2.09], partial response was 1.18 [95%CI: 0.87-1.61], overall response was 1.20 [95%CI: 0.93-1.56], stable disease was 1.09 [95%CI: 0.78-1.53], progressive disease was 0.80 [95%CI: 0.74 to 0.87], and clinical benefit was 1.08 [95%CI: 0.80-1.49]. For safety parameters, pooled RR for hyperglycemia was 4.57 [95%CI: 3.15-6.62], and gastrointestinal toxicity was 1.82 [95%CI: 1.56 to 2.14].
CONCLUSION
PI3K inhibitors had better efficacy than the present standard of concern for patients with breast cancer, especially among patients with PIK3CA mutations. Hence, clinicians and oncologists can provide this drug for the target population with extra caution for diabetes patients.
PubMed: 38275057
DOI: 10.2174/0115680096266181231207110048 -
Reproductive Sciences (Thousand Oaks,... Jan 2024As a public health problem, premature ovarian insufficiency leads to infertility or sub-fertility. In addition to premature ovarian insufficiency (POI) increases the... (Meta-Analysis)
Meta-Analysis
As a public health problem, premature ovarian insufficiency leads to infertility or sub-fertility. In addition to premature ovarian insufficiency (POI) increases the lifetime risk of bone fragility, cardiovascular disease, and cognitive impairment. To investigate the effects of environmental pollutants on the occurrence of POI and explore its mechanism, we conducted a computer search for articles published in electronic databases by December 13, 2022. Three reviewers independently examined all included studies and scored the qualities of included studies using the Newcastle-Ottawa Scale criteria. In this meta-analysis, eight clinical studies as well as ten preclinical findings showed a pooled OR of 2.331 and 95% CI of 1.968-2.760. This confirms that environmental pollutants, including POPs, heavy metals, PAEs, PAHs, cosmetic and pharmaceutical products, and cigarette smoke, are indeed significant risk factors for POI. In addition, it is demonstrated from the results of this study that signaling pathway of calcium and PI3K Akt and Xpnpep2, Col1, Col3, Col4, Cx43, Egr3, Tff1, and Ptgs2 genes may all be involved in the process. Environmental pollutants, including POPs, heavy metals, PAEs, PAHs, cosmetic and pharmaceutical products, and cigarette smoke, are indeed significant risk factors for POI.
Topics: Female; Humans; Environmental Pollutants; Phosphatidylinositol 3-Kinases; Primary Ovarian Insufficiency; Menopause, Premature; Infertility; Metals, Heavy; Pharmaceutical Preparations
PubMed: 37612521
DOI: 10.1007/s43032-023-01326-5