Study on the sensitizing effect of SM-1 combined with irradiation on head and neck squamous cell carcinoma.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is globally prevalent with high recurrence, low survival rate, and poor quality of life for patients. Derived from PAC-1, SM-1 can activate procaspase-3 and induce apoptosis in cancer cells to exert anti-tumor effects. However, the inhibitory effect of SM-1 on HNSCC after combination with radiation are unclear. This study aims to investigate the radiosensitizing effect of SM-1 on HNSCC in vitro and in vivo. METHODS: MTT method was used to detect the effect of SM-1 on the viability of HNSCC cell lines (HONE1, HSC-2, and CAL27). The effects of SM-1 combined with radiation on the survival index of HONE1, HSC-2, and CAL27 cell lines were determined by colony formation assay. Flow cytometry was used to investigate the effects of SM-1 and radiation combination on cell apoptosis and cell cycle, and western blot experiments were performed to detect the expression of apoptosis and cell cycle-related proteins. Finally, a xenograft tumor model of CAL27 was established to evaluate the anti-tumor effect of SM-1 combined with radiation in vivo. RESULTS: In vitro, SM-1 effectively inhibited the activity of HNSCC cell lines HONE1, HSC-2, and CAL27 cells, and synergistically showed anti-proliferation activity during combined irradiation. Meanwhile, anti-tumor effect of SM-1 on HNSCC was higher than that of Debio1143, and the radiosensitivity of cells was greatly increased. Flow cytometry and western blot analysis showed that SM-1 induced G2/M phase arrest of head and neck squamous cell carcinoma cells via inhibiting the expression of CyclinB1 and CDC2. Moreover, SM-1 activated caspase-3 activity and up-regulated the cleaved form of PARP1 to induce cell apoptosis. In vivo, SM-1 combined irradiation showed a good anti-tumor effect. CONCLUSION: SM-1 enhances HNSCC cell radiation sensitivity in vitro and in vivo, supporting its potential as a radiosensitizer for clinical trials in combination with radiotherapy.

Design, synthesis, and evaluation of novel stilbene derivatives that degrade acidic nucleoplasmic DNA-binding protein 1 (And1) and synergize with PARP1 inhibitor in NSCLC cells.

Specifically inducing the degradation of acidic nucleoplasmic DNA-binding protein 1 (And1) is a promising antitumor strategy. Our previous study identified Bazedoxifene (BZA) and CH3 as specific And1 degraders and validated their activity in reversing radiotherapy resistance in vitro and in vivo. However, unelucidated structure-activity relationships and moderate activity have limited their application. In this study, 27 novel CH3 derivatives were designed and synthesised based on the cavity topology of the WD40 domain of And1. Among them, A15 with a "V" conformation significantly induced And1 degradation in NSCLC cells. In addition, this study demonstrated a potential synthetic lethal effect of And1 degraders and PARP1 inhibitors. 1 µM of Olaparib in combination with 5 µM of A15 significantly inhibited the proliferation of A549 and H460 cells. Overall, these compounds are valuable tools for elucidating And1 biology, and their special spatial conformation make them promising candidates for future optimisation studies.

Ionizing radiation induces neurotoxicity in Xenopus laevis embryos through neuroactive ligand-receptor interaction pathway.

Ionizing radiation (IR) poses a significant threat to both the natural environment and biological health. Exposure to specific doses of ionizing radiation early in an organism's development can lead to developmental toxicity, particularly neurotoxicity. Through experimentation with Xenopus laevis (X. laevis), we examined the effects of radiation on early developmental stage. Our findings revealed that radiation led to developmental abnormalities and mortality in X. laevis embryos in a dose-dependent manner, disrupting redox homeostasis and inducing cell apoptosis. Additionally, radiation caused neurotoxic effects, resulting in abnormal behavior and neuron damage in the embryos. Further investigation into the underlying mechanisms of radiation-induced neurotoxicity indicated the potential involvement of the neuroactive ligand-receptor interaction pathway, which was supported by RNA-Seq analysis. Validation of gene expression associated with this pathway and analysis of neurotransmitter levels confirmed our hypothesis. In addition, we further validated the important role of this signaling pathway in radiation-induced neurotoxicity through edaravone rescue experiments. This research establishes a valuable model for radiation damage studying and provides some insight into radiation-induced neurotoxicity mechanisms.

Novel CDK19-Targeted Radiotracers: A Potential Design Strategy to Improve the Pharmacokinetics and Tumor Uptake.

Cyclin-dependent kinase 19 (CDK19) is overexpressed in prostate cancer, making it an attractive target for both imaging and therapy. Since little is known about the optimized approach for radioligands of nuclear proteins, linker optimization strategies were used to improve pharmacokinetics and tumor absorption, including the adjustment of the length, flexibility/rigidity, and hydrophilicity/lipophilicity of linkers. Molecular docking was conducted for virtual screening and followed by IC50 determination. Both BALB/c mice and P-16 xenografts were used for tissue distribution and PET/CT imaging. The ligand 68Ga-10c demonstrated high absorption in tumor 5 min after injection and sustains long-term imaging within 3 h. Furthermore, 68Ga-10c exhibited slow clearance within the tumor and was predominantly metabolized in both the liver and kidneys, showing the potential to alleviate metabolic pressure and enhance tissue safety. Therefore, the linker optimization strategy is well suited for CDK19 and provides a reference for the radioactive ligands of other nuclear targets.

Downregulation of UBB potentiates SP1/VEGFA-dependent angiogenesis in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) presents a unique profile characterized by high levels of angiogenesis and robust vascularization. Understanding the underlying mechanisms driving this heterogeneity is essential for developing effective therapeutic strategies. This study revealed that ubiquitin B (UBB) is downregulated in ccRCC, which adversely affects the survival of ccRCC patients. UBB exerts regulatory control over vascular endothelial growth factor A (VEGFA) by directly interacting with specificity protein 1 (SP1), consequently exerting significant influence on angiogenic processes. Subsequently, we validated that DNA methyltransferase 3 alpha (DNMT3A) is located in the promoter of UBB to epigenetically inhibit UBB transcription. Additionally, we found that an unharmonious UBB/VEGFA ratio mediates pazopanib resistance in ccRCC. These findings underscore the critical involvement of UBB in antiangiogenic therapy and unveil a novel therapeutic strategy for ccRCC.

Bazedoxifene analogs as potential WDHD1 degraders and antitumor agents: Synthesis, evaluation and molecular dynamics simulation studies.

DNA repair is strongly associated with tumor resistance to radiotherapy and chemotherapy. WD repeat and HMG-box DNA binding protein 1 (WDHD1) is a key adaptor for homologous recombination repair of DNA, and its overexpression is relevant to the poor prognosis of many tumor patients. We previously have identified and validated bazedoxifene (BZA), which had 60% inhibitory rate on WDHD1 in MCF7 cells at 10 µM, from the Food and Drug Administration-approved compound library. Here, we initially established the binding model of BZA, synthesized and evaluated eight BZA analogs. Further, we detailed the use of molecular dynamics simulations to provide insights into the basis for activity against WDHD1. This binding mode will be instructive for the development of new WDHD1 degraders.

SREBP inhibitors: an updated patent review for 2008-present.

INTRODUCTION: Sterol regulatory element-binding proteins (SREBPs) are a family of membrane-binding transcription factors that activate genes encoding enzymes required for cholesterol and unsaturated fatty acid synthesis. Overactivation of SREBP is related to the occurrence and development of diabetes, nonalcoholic fatty liver, tumor, and other diseases. In the past period, many SREBP inhibitors have been found. AREAS COVERED: This manuscript is a patent review of SREBP inhibitors. We searched 2008 to date for all data from the US patent database (https://www.uspto.gov/) and the European patent database (https://www.epo.org/) with 'SREBP' and 'inhibitor' as keywords and analyzed the search results. EXPERT OPINION: Both synthetic and natural SREBP inhibitors have been reported. Despite the lack of cocrystal structure of SREBP inhibitor, the mechanisms of several compounds have been clarified. Importantly, some SREBP inhibitors have been proved to have good activity in preclinical studies. As the characteristics of lipid metabolism reprogramming in cardio-cerebrovascular diseases and tumors are gradually revealed, more and more attention will be focused on SREBP.

Erratum: Author correction to 'Discovery of the radio-protecting effect of ecliptae herba, its constituents and targeting p53-mediated apoptosis in vitro and in vivo' [Acta Pharm Sin B 13 (2023) 1216-1230].

[This corrects the article DOI: 10.1016/j.apsb.2022.09.003.].

[Research progress in prevention and treatment of radiation-induced intestinal injury by traditional Chinese medicine active components].

Radiation-induced intestinal injury(RIII), a common complication of radiotherapy for pelvic malignancies, affects the quality of life and the radiotherapy efficacy for cancer. Currently, the main clinical approaches for the prevention and treatment of RIII include drug therapy, hyperbaric oxygen therapy, and surgical treatment. Among these methods, drug therapy is cost-effective. Traditional Chinese medicine(TCM) containing a variety of active components demonstrates mild side effects and good efficacy in preventing and treating RIII. Studies have proven that TCM active components, such as flavonoids, terpenoids, phenylpropanoids, and alkaloids, can protect the intestine against RIII by inhibiting oxidative stress, regulating the expression of inflammatory cytokines, modulating the mitochondrial apoptosis pathway, adjusting intestinal flora, and suppressing cell apoptosis. These mechanisms can help alleviate the symptoms of RIII. The paper aims to provide a theoretical reference for the discovery of new drugs for the prevention and treatment of RIII by reviewing the literature on TCM active components in the last 10 years.

PET imaging of new target CDK19 in prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) is a superior method to predict patients' risk of cancer progression and response to specific therapies. However, its performance is limited for neuroendocrine prostate cancer (NEPC) and PSMA-low prostate cancer cells, resulting in diagnostic blind spots. Hence, identifying novel specific targets is our aim for diagnosing those prostate cancers with low PSMA expression. METHODS: The Cancer Genome Atlas (TCGA) database and our cohorts from men with biopsy-proven high-risk metastatic prostate cancer were used to identify CDK19 and PSMA expression. PDX lines neP-09 and P-16 primary cells were used for cellular uptake and imaging mass cytometry in vitro. To evaluate in vivo CDK19-specific uptake of gallium(Ga)-68-IRM-015-DOTA, xenograft mice models and blocking assays were used. PET/CT imaging data were obtained to estimate the absorbed dose in organs. RESULTS: Our study group had reported the overexpression of a novel tissue-specific gene CDK19 in high-risk metastatic prostate cancer and CDK19 expression correlated with metastatic status and tumor staging, independently with PSMA and PSA levels. Following up on this new candidate for use in diagnostics, small molecules targeting CDK19 labeled with Ga-68 (68Ga-IRM-015-DOTA) were used for PET in this study. We found that the 68Ga-IRM-015-DOTA was specificity for prostate cancer cells, but the other cancer cells also took up little 68Ga-IRM-015-DOTA. Importantly, mouse imaging data showed that the NEPC and CRPC xenografts exhibited similar signal strength with 68Ga-IRM-015-DOTA, but 68Ga-PSMA-11 only stained the CRPC xenografts. Furthermore, target specificity was elucidated by a blocking experiment on a CDK19-bearing tumor xenograft. These data concluded that 68Ga-CDK19 PET/CT was an effective technology to detect lesions with or without PSMA in vitro, in vivo, and in the PDX model. CONCLUSION: Thus, we have generated a novel PET small molecule with predictive value for prostate cancer. The findings indicate that 68Ga-CDK19 may merit further evaluation as a predictive biomarker for PET scans in prospective cohorts and may facilitate the identification of molecular types of prostate cancer independent of PSMA.

Discovery of the radio-protecting effect of Ecliptae Herba, its constituents and targeting p53-mediated apoptosis in vitro and in vivo.

Radiation protection drugs are often accompanied by toxicity, even amifostine, which has been the dominant radio-protecting drug for nearly 30 years. Furthermore, there is no therapeutic drug for radiation-induced intestinal injury (RIII). This paper intends to find a safe and effective radio-protecting ingredient from natural sources. The radio-protecting effect of Ecliptae Herba (EHE) was discovered preliminarily by antioxidant experiments and the mouse survival rate after 137Cs irradiation. EHE components and blood substances in vivo were identified through UPLC‒Q-TOF. The correlation network of "natural components in EHE-constituents migrating to blood-targets-pathways" was established to predict the active components and pathways. The binding force between potential active components and targets was studied by molecular docking, and the mechanism was further analyzed by Western blotting, cellular thermal shift assay (CETSA), and ChIP. Additionally, the expression levels of Lgr5, Axin2, Ki67, lysozyme, caspase-3, caspase-8,8-OHdG, and p53 in the small intestine of mice were detected. It was found for the first time that EHE is active in radiation protection and that luteolin is the material basis of this protection. Luteolin is a promising candidate for RⅢ. Luteolin can inhibit the p53 signaling pathway and regulate the BAX/BCL2 ratio in the process of apoptosis. Luteolin could also regulate the expression of multitarget proteins related to the same cell cycle.

Protective effect of total flavonoids of Engelhardia roxburghiana Wall. leaves against radiation-induced intestinal injury in mice and its mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Irradiation-induced intestinal injury (RIII) often occurs during radiotherapy in patients, which would result in abdominal pain, diarrhea, nausea, vomiting, and even death. Engelhardia roxburghiana Wall. leaves, a traditional Chinese herb, has unique anti-inflammatory, anti-tumor, antioxidant, and analgesic effects, is used to treat damp-heat diarrhea, hernia, and abdominal pain, and has the potential to protect against RIII. AIM OF THE STUDY: To explore the protective effects of the total flavonoids of Engelhardia roxburghiana Wall. leaves (TFERL) on RIII and provide some reference for the application of Engelhardia roxburghiana Wall. leaves in the field of radiation protection. MATERIALS AND METHODS: The effect of TFERL on the survival rate of mice was observed after a lethal radiation dose (7.2 Gy) by ionizing radiation (IR). To better observe the protective effects of the TFERL on RIII, a mice model of RIII induced by IR (13 Gy) was established. Small intestinal crypts, villi, intestinal stem cells (ISC) and the proliferation of ISC were observed by haematoxylin and eosin (H&E) and immunohistochemistry (IHC). Quantitative real-time PCR (qRT-PCR) was used to detect the expression of genes related to intestinal integrity. Superoxide dismutase (SOD), reduced glutathione (GSH), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum of mice were assessed. In vitro, cell models of RIII induced by IR (2, 4, 6, 8 Gy) were established. Normal human intestinal epithelial cells HIEC-6 cells were treated with TFERL/Vehicle, and the radiation protective effect of TFERL on HIEC-6 cells was detected by clone formation assay. DNA damage was detected by comet assay and immunofluorescence assay. Reactive oxygen species (ROS), cell cycle and apoptosis rate were detected by flow cytometry. Oxidative stress, apoptosis and ferroptosis-related proteins were detected by western blot. Finally, the colony formation assay was used to detect the effect of TFERL on the radiosensitivity of colorectal cancer cells. RESULTS: TFERL treatment can increase the survival rate and time of the mice after a lethal radiation dose. In the mice model of RIII induced by IR, TFERL alleviated RIII by reducing intestinal crypt/villi structural damage, increasing the number and proliferation of ISC, and maintaining the integrity of the intestinal epithelium after total abdominal irradiation. Moreover, TFERL promoted the proliferation of irradiated HIEC-6 cells, and reduced radiation-induced apoptosis and DNA damage. Mechanism studies have found that TFERL promotes the expression of NRF2 and its downstream antioxidant proteins, and silencing NRF2 resulted in the loss of radioprotection by TFERL, suggesting that TFERL exerts radiation protection by activating the NRF2 pathway. Surprisingly, TFERL reduced the number of clones of colon cancer cells after irradiation, suggesting that TFERL can increase the radiosensitivity of colon cancer cells. CONCLUSION: Our data showed that TFERL inhibited oxidative stress, reduced DNA damage, reduced apoptosis and ferroptosis, and improved IR-induced RIII. This study may offer a fresh approach to using Chinese herbs for radioprotection.

Corrigendum: Exploring the pharmacological mechanisms of icaritin against nasopharyngeal carcinoma via network pharmacology and experimental validation.

[This corrects the article DOI: 10.3389/fphar.2022.993022.].

Chinese herbal medicine for drug-induced liver injury in patients with HIV/AIDS: A systematic review of randomized controlled trials.

Background: To explore the effectiveness and safety of Chinese herbal medicine (CHM) for drug-induced liver injury (DILI) in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Methods: A systematic search was made of eight databases (Pubmed, Cochrane Library, Web of Science, Embase, CNKI, Wanfang, VIP, Sinomed) and two trial registries (WHO ICTRP, ClinicalTrials.gov) from inception to September 2022. The effect size was presented as risk ratio (RR) or mean difference (MD) with their 95% confidence interval (CI). The Cochrane Risk of Bias and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tools were used for quality appraisal. Results: Ten randomized controlled trials (RCTs) involving 732 participants were included. Comparing CHM alone with routine treatment, the CHM group showed lower aspartate aminotransferase (MD=-11.47 U/L, 95%CI[-13.05, -9.89], low certainty), lower alanine aminotransferase (MD=-2.68 U/L, 95%CI[-4.27, -1.08], low certainty), lower total bilirubin (MD=-4.31 mmol/L, 95%CI[-5.66, -2.96], low certainty), lower bilirubin direct (MD=-3.19 mmol/L, 95%CI[-3.87, -2.51], low certainty), and higher effective rate (assessed by symptoms and liver indicators) (RR=1.13, 95%CI[1.06, 1.20], low certainty). A significant difference was also found in CHM plus routine treatment versus routine treatment in the previous outcomes. No significant difference was found on helper T cells among these comparisons. Only one RCT reported safety of CHM and found no adverse reaction during the trial. Conclusions: CHM may improve the liver function indices and effective rate for HIV/AIDS patients with DILI. However, the sample size was small and quality was low. Larger-samples of high-quality trials are needed.

The categorizations of vasculogenic mimicry in clear cell renal cell carcinoma unveil inherent connections with clinical and immune features.

Background: Clear cell renal cell carcinoma (ccRCC) stands as the prevailing variant kidney cancer in humans. Unfortunately, patients with disseminated RCC at diagnosis often have a diminished prognosis. Rapid tumor growth necessitates efficient blood supply for oxygen and nutrients, involving the circulation of blood from vessels to tumor tissues, facilitating tumor cell entry into the extracellular matrix. Vasculogenic mimicry (VM) significantly contributes to tumor growth and metastasis. Within this investigation, we identified vasculogenic mimicry-related genes (VMRGs) by analyzing data from 607 cases of kidney renal clear cell carcinoma (KIRC) in The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). These findings offer insights into ccRCC progression and metastasis. Method: We identified VMRGs-related subtypes using consistent clustering methods. The signature of the VMRGs was created using univariate Cox regression and LASSO Cox regression analyses. To evaluate differences in immune cell infiltration, we employed ssGSEA. Afterwards, we created an innovative risk assessment model, known as the VM index, along with a nomogram to forecast the prognosis of ccRCC. Additionally, we verified the expression of an important gene related to VM, peroxiredoxin 2 (PRDX2), in tissue samples. Furthermore, we assessed the sensitivity to drugs in various groups by utilizing the pRRophetic R package. Results: Significant predictors of survival rates in both high- and low-risk groups of KIRC patients were identified as VMRGs. The independent prognostic factors for RCC were confirmed by both univariate and multivariate Cox regression analyses, validating VMRG risk signatures. Differences were observed in drug sensitivity, immune checkpoint expression, and responses to immune therapy between patients classified into high- and low-VMRG-risk groups. Our nomograms consistently demonstrated precise predictive capabilities. Finally, we experimentally verified PRDX2 expression levels and their impact on prognosis. Conclusion: The signature predicts patient prognosis and therapy response, laying the groundwork for future clinical strategies in treating ccRCC patients.

Exploring the pharmacological mechanisms of icaritin against nasopharyngeal carcinoma via network pharmacology and experimental validation.

Background: Icaritin is a natural product with a wide range of anti-tumor effects. However, its anti-tumor mechanism has not been thoroughly studied. This study examined the inhibitory effect of icaritin on nasopharyngeal cancer and its underlying mechanism using network pharmacology along with in vivo and in vitro experiments. Methods: MTT and clone formation assays were used to detect the effects of icaritin on the viability and proliferation of nasopharyngeal carcinoma cells, followed by the construction of a HONE1 xenograft tumor model to evaluate the anti-tumor efficacy of icaritin in vivo. A public database was used to predict prospective targets, built a protein-protein interaction (PPI) network, and analyze gene enrichment and biological processes. Based on network pharmacological data, cell cycle-related proteins were identified using western blotting. Besides, cell cycle distribution, apoptosis, and intracellular reactive oxygen species (ROS) generation were identified using flow cytometry. In addition, SA-ß-Gal staining was performed to detect cellular senescence, and western blotting was performed to detect the expression of P53, P21, and other proteins to verify key signaling pathways. Results: Icaritin effectively inhibited the viability and proliferation of nasopharyngeal carcinoma cell lines and showed good anti-tumor activity against HONE1 nasopharyngeal carcinoma cells in vivo. Key protein targets, including AKT1, HSP90AA1, CDK4, CCND1, and EGFR, were screened using PPI network topology analysis. GO and KEGG analysis revealed that the cell cycle, p53 signaling, and cell senescence pathways may be the main regulatory pathways. Flow cytometry and western blot experiments showed that icaritin caused S-phase arrest and promoted an increase in ROS. SA-ß-Gal staining showed that icaritin significantly induced cellular senescence, and western blotting showed that the expression of senescence-related proteins p53 and P21 increased significantly. Moreover, inhibition of ROS levels by N-Acetylcysteine (NAC) enhanced cell viability, reversed cellular senescence and reduced cellular senescence-associated protein expression. Conclusion: The results of network pharmacological analysis and in vivo and in vitro experiments showed that icaritin effectively inhibited the growth of nasopharyngeal carcinoma cells, promoted ROS production, induced cellular senescence, and inhibited tumor cells, which are related to the regulation of P53/P21 signal pathway.

Molecular mechanisms of isoflavone puerarin against cardiovascular diseases: What we know and where we go.

Puerarin (Pue), known as a phytoestrogen, has salient bioactivities and is promising against cardiovascular diseases. This article summarizes the underlying molecular mechanisms of Pue in treating cardiovascular diseases, especially regulating the intracellular signal transduction, influencing ion channels, modulating the expression of microRNA, and impacting on the autophagy, which are mainly involved in the inflammatory signaling pathways, fatty acid/lipid metabolism, oxidative stress, apoptosis, and the like. The protective effect of Pue against cardiovascular diseases mainly involves attenuating the myocardial injury and decreasing the myocardial fibrosis, improving the myocardial ischemia/reperfusion injury, as well as inhibiting the myocardial hypertrophy and atherosclerosis. The molecular mechanisms of Pue's cardiovascular protective effects for the first time and comment on the state-of-the-art research methods and principles of Pue's regulation of small molecules were reviewed, so as to provide the rationale for its basic research and clinical applications.

Acupuncture for cancer-related conditions: An overview of systematic reviews.

BACKGROUND: Acupuncture is commonly used for cancer-related conditions worldwide, and evidence is increasing year on year. There is a need to summarize the evidence of acupuncture for cancer-related conditions comprehensively and critically. OBJECTIVE: To evaluate and summarize the systematic reviews (SRs) that assess the effects and safety of acupuncture for cancer-related conditions, and to inform clinical practice and future studies. METHODS: A comprehensive search was conducted on Pubmed, Embase, the Cochrane Library, Web of Science, CNKI, VIP, Sinomed, and Wanfang from their inception to October 16, 2021. SRs of randomized controlled trials (RCTs) on acupuncture for cancer-related conditions were to be included. Two reviewers screened the eligible articles, and four reviewers in pair extracted data and assessed the methodological quality/risk of bias of all included reviews by AMSTAR 2 and ROBIS tools. The overlap of primary studies was measured by calculating corrected covered areas. Data from the included reviews were synthesized with a summary of meta-analysis or narrative description. RESULTS: Fifty-one SRs of RCTs on acupuncture for cancer-related conditions were included and synthesized. The methodological quality of SRs included 1 "high", 5 "low" and 45 "very low" by AMSTAR 2. Sixteen SRs assessed as low risk of bias (31.37%), and 35 SRs had high risk of bias (68.63%) by ROBIS. Acupuncture showed effective on systemic conditions in relation to different cancers, including cancer-related pain (17 SRs, 80 RCTs), fatigue (7 SRs, 18 RCTs), insomnia (4 SRs, 10 RCTs), quality of life (2 SRs, 15 RCTs); conditions in relation to chemo-radiotherapy, including nausea and vomiting (3 SRs, 36 RCTs) and bone marrow suppression (2 SRs, 21 RCTs); and conditions in relation to specific cancers, including breast cancer-related menopause (3 SRs, 6 RCTs), hot flashes (12 SRs, 13 RCTs), arthralgia (5 SRs, 10 RCTs), and nasopharyngeal cancer-related dysphagia (1 SRs, 7 RCTs). Acupuncture appeared to have benefit for patients with lymphoedema (3 SRs, 3 RCTs), gastrointestinal function (5 SRs, 27 RCTs), and xerostomia (4 SRs, 7 RCTs). Limited evidence showed inconsistent results on acupuncture for chemotherapy-induced peripheral neuropathy (3 SRs, 6 RCTs), depression and anxiety (3 SRs, 9 RCTs). Acupuncture was regarded as a safe therapy for cancer patients as no severe adverse events related were reported. CONCLUSION: Evidence from SRs showed that acupuncture is beneficial to cancer survivors with cancer-related pain, fatigue, insomnia, improved quality of life, nausea and vomiting, bone marrow suppression, menopausal symptoms, arthralgia, and dysphagia, and may also be potential for lymphoedema, gastrointestinal function, and xerostomia. For neuropathy, depression and anxiety, acupuncture should be used as an option based on individual conditions. Acupuncture is relatively safe without serious adverse events. More well-designed clinical trials of acupuncture are recommended on cancer-related depression and anxiety, arthralgia, xerostomia, gastrointestinal dysfunction and dysphagia.

The clinical significance, immune infiltration, and tumor mutational burden of angiogenesis-associated lncRNAs in kidney renal clear cell carcinoma.

Background: Poor prognosis of kidney renal clear cell carcinoma (KIRC) is often related to angiogenesis. The lncRNAs that regulate angiogenesis could also affect the prognosis of KIRC. It is meaningful for us to use lncRNAs related to angiogenesis to construct a generic, individualized prognostic signature for patients with KIRC. Methods: We identified eight angiogenesis-associated genes (AAGs) by differential expression analysis and univariate Cox regression from The Cancer Genome Atlas dataset, including 537 KIRC samples and 72 normal samples. In total, 23 prognostic lncRNAs were screened out after Pearson correlation analysis and univariate Cox regression analysis. Then, we performed least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression to establish a four-AAG-related lncRNA prognostic signature. Results: The risk score was calculated for each KIRC patients by using a four-AAG-related lncRNA prognostic signature. We divided the KIRC patients into high- and low-risk groups by the median of the risk score. It was confirmed that the AAG-related lncRNA prognostic signature has good prognostic value for KIRC patients by time-dependent receiver operating characteristic and Kaplan-Meier survival analysis. We identified 3,399 differentially expressed genes between the high- and low-risk groups and performed their functional enrichment analyses. The AAG-related lncRNA prognostic signature was an independent prognostic predictor for KIRC patients and was used to perform a combined nomogram. We reevaluated them in terms of survival, clinic characteristics, tumor-infiltrating immune cells and tumor mutation burden. Conclusion: Our research indicates that the AAG-related lncRNA prognostic signature is a promising and potential independent prognostic indicator for KIRC patients. Then, it could offer new insights into the prognosis assessment and potential treatment strategies of KIRC patients.

Discovery of Natural Ursane-type SENP1 Inhibitors and the Platinum Resistance Reversal Activity Against Human Ovarian Cancer Cells: A Structure-Activity Relationship Study.

Platinum-resistant ovarian cancer is one of the most common and refractory gynecologic cancers around the world. The SENP1/JAK2 (small ubiquitin-like modifier-specific protease 1/Janus activating kinase 2) axis activation has been proposed as a critical mechanism in platinum-resistant ovarian cancer, and as such, SENP1 inhibitors become a feasible alternative to reverse platinum resistance. In this work, 29 commercially available natural ursane-type aglycones were tested for their SENP1 inhibitory activities, among which 12 aglycones showed IC50 activity at the concentration below 5 µM. Pomolic acid and tormentic acid were identified as potent SENP1 inhibitors with the IC50 values of 5.1 and 4.3 µM, respectively. The structure-activity relationship (SAR) of ursane-type SENP1 inhibitors was evaluated. A molecular docking model of the SENP1-tormentic acid complex was obtained and applied to describe the SAR. Moreover, the combinations of cisplatin with pomolic acid (IC50 = 3.69 µM, combination index (CI) = 0.23) and tormentic acid (IC50 = 2.40 µM, CI = 0.30) exhibited potent platinum-resistant reversal activities to cisplatin only (IC50 = 28.23 µM) against the human ovarian cancer SKOV3 cells. The data suggested a potential for pomolic acid and tormentic acid to be promising compounds for in vivo studies of platinum-resistant ovarian cancer with SENP1 activation.