Schistosomiasis is a neglected zoonotic parasitic disease. Currently, praziquantel is the drug of choice for the treatment of schistosomiasis, and is the only effective chemical for treatment of schistosomiasis japonica. Since its introduction in the 1970s, praziquantel has been used for large-scale chemotherapy of schistosomiasis for over 40 years. However, there have been reports pertaining to the resistance to praziquantel in schistosomes. Therefore, development of novel antischistosomal agents as alternatives of praziquantel, is of great need. Histone deacetylases and histone acetyltransferases have been recently reported to play critical roles in the growth, development and reproduction of schistosomes, and are considered as potential drug targets for the treatment of schistosomiasis. This review summarizes the latest advances of histone deacetylase and histone acetyltransferase inhibitors in the research on antischistosomal drugs, so as to provide insights into research and development of novelantischistosomal agents.
［摘要］ 血吸虫病是一种被忽视的人兽共患寄生虫病。目前, 吡喹酮是治疗血吸虫病的首选药物, 也是治疗日本血吸虫 病的唯一有效药物。自 20 世纪 70 年代问世以来, 吡喹酮已在大规模血吸虫病化疗中应用了 40 余年, 长期大规模使用导 致部分地区血吸虫对其产生了抗性, 因此迫切需要研发新型抗血吸虫药物作为候选替代药物。近期研究表明, 组蛋白去 乙酰化酶和组蛋白乙酰转移酶在血吸虫的生长发育以及繁殖等阶段中均起关键作用, 被认为是治疗血吸虫病的潜在药 物靶点。本文总结了组蛋白去乙酰化酶抑制剂与组蛋白乙酰转移酶抑制剂在抗血吸虫药物研究中的最新进展, 以期为 抗血吸虫新药的研发提供参考。.

UNASSIGNED: The overall survival of peripheral T-cell lymphoma (PTCL) is dismal. Histone deacetylase (HDAC) inhibitors have exhibited promising treatment outcomes for PTCL patients. Therefore, this work aims to systematically evaluate the treatment outcome and safety profile of HDAC inhibitor-based treatment for untreated and relapsed/refractory (R/R) PTCL patients.
UNASSIGNED: The prospective clinical trials of HDAC inhibitors for the treatment of PTCL were searched on the Web of Science, PubMed, Embase, ClinicalTrials.gov, and Cochrane Library database. The pooled overall response rate, complete response (CR) rate, and partial response rate were measured. The risk of adverse events was evaluated. Moreover, the subgroup analysis was utilized to assess the efficacy among different HDAC inhibitors and efficacy in different PTCL subtypes.
UNASSIGNED: For untreated PTCL, 502 patients in seven studies were involved, and the pooled CR rate was 44% (95% CI, 39-48%). For R/R PTCL patients, there were 16 studies included, and the CR rate was 14% (95% CI, 11-16%). The HDAC inhibitor-based combination therapy exhibited better efficacy when compared with HDAC inhibitor monotherapy for R/R PTCL patients (P = 0.02). In addition, the pooled CR rate was 17% (95% CI, 13-22%), 10% (95% CI, 5-15%), and 10% (95% CI, 5-15%) in the romidepsin, belinostat, and chidamide monotherapy subgroups, respectively. In the R/R angioimmunoblastic T-cell lymphoma subgroup, the pooled ORR was 44% (95% CI, 35-53%), higher than other subtypes. A total of 18 studies were involved in the safety assessment of treatment-related adverse events. Thrombocytopenia and nausea were the most common hematological and non-hematological adverse events, respectively.
UNASSIGNED: This meta-analysis demonstrated that HDAC inhibitors were effective treatment options for untreated and R/R PTCL patients. The combination of HDAC inhibitor and chemotherapy exhibited superior efficacy to HDAC inhibitor monotherapy in the R/R PTCL setting. Additionally, HDAC inhibitor-based therapy had higher efficacy in angioimmunoblastic T-cell lymphoma patients than that in other subtypes.

Maintenance therapy in adult T-cell acute lymphoblastic leukemia (T-ALL) is the longest phase but with limited option. The classic drugs used in the maintenance phase such as 6-mercaptopurine, methotrexate, corticosteroid and vincristine have potentially serious toxicities. Optimizing therapy in the modern age, chemo-free maintenance therapy regimens for patients with T-ALL may dramatically improve the maintenance therapeutic landscape. We report here the combination of Anti-programmed cell death protein 1 antibody and histone deacetylase inhibitor as chemo-free maintenance treatment in a T-ALL patient with literature review, thus providing a unique perspective in addition to valuable information which may inform novel therapeutic approaches.

UNASSIGNED: Histone deacetylase inhibitors (HDACi) including valproic acid (VPA) have the potential to improve radiotherapy (RT) efficacy and reduce treatment adverse events (AE) via epigenetic modification and radio-sensitization of neoplastic cells. This systematic review and meta-analysis aimed to assess the efficacy and AE associated with HDACi used as radio-sensitizers in adult solid organ malignancy patients.
UNASSIGNED: A systematic review utilized electronic searches of MEDLINE(Ovid), Embase(Ovid), The Cochrane Library, and the International Clinical Trials Registry Platform to identify studies examining the efficacy and AEs associated with HDACi treatment in solid organ malignancy patients undergoing RT. Meta-analysis was performed with overall survival (OS) reported as hazard ratios (HR) as the primary outcome measure. OS reported as median survival difference, and AEs were secondary outcome measures.
UNASSIGNED: Ten studies reporting on the efficacy and/or AEs of HDACi in RT-treated solid organ malignancy patients met inclusion criteria. All included studies focused on HDACi valproic acid (VPA) in high-grade glioma patients, of which 9 studies (n = 6138) evaluated OS and 5 studies (n = 1055) examined AEs. The addition of VPA to RT treatment protocols resulted in improved OS (HR = 0.80, 95% CI 0.67-0.96). No studies focusing on non-glioma solid organ malignancy patients, or non-VPA HDACi met the inclusion criteria for this review.
UNASSIGNED: This review suggests that glioma patients undergoing RT may experience prolonged survival due to HDACi VPA administration. Further randomized controlled trials are required to validate these findings. Additionally, more research into the use of HDACi radio-adjuvant treatment in non-glioma solid organ malignancies is warranted.

The marine environment is highly diverse, each living creature fighting to establish and proliferate. Among marine organisms, cyanobacteria are astounding secondary metabolite producers representing a wonderful source of biologically active molecules aimed to communicate, defend from predators, or compete. Studies on these molecules\' origins and activities have been systematic, although much is still to be discovered. Their broad chemical diversity results from integrating peptide and polyketide synthetases and synthases, along with cascades of biosynthetic transformations resulting in new chemical structures. Cyanobacteria are glycolipid, macrolide, peptide, and polyketide producers, and to date, hundreds of these molecules have been isolated and tested. Many of these compounds have demonstrated important bioactivities such as cytotoxicity, antineoplastic, and antiproliferative activity with potential pharmacological uses. Some are currently under clinical investigation. Additionally, conventional chemotherapeutic treatments include drugs with a well-known range of side effects, making anticancer drug research from new sources, such as marine cyanobacteria, necessary. This review is focused on the anticancer bioactivities of metabolites produced by marine cyanobacteria, emphasizing the identification of each variant of the metabolite family, their chemical structures, and the mechanisms of action underlying their biological and pharmacological activities.

Isocitrate dehydrogenase (IDH) mutations are present in 70% of World Health Organization grade II and III gliomas. IDH mutation induces accumulation of the oncometabolite 2-hydroxyglutarate. Therefore, therapies targeting reversal of epigenetic dysregulation in gliomas have been suggested. However, the utility of epigenetic treatments in gliomas remains unclear. Here, we present the first clinical systematic review of epigenetic therapies in treatment of IDH-mutant gliomas and highlight their safety and efficacy.
We conducted a systematic search of electronic databases from 2000 to January 2021 following PRISMA guidelines. Articles were screened to include clinical usage of epigenetic therapies in case reports, prospective case series, or clinical trials. Primary and secondary outcomes included safety/tolerability of epigenetic therapies and progression-free survival/overall survival, respectively.
A total of 133 patients across 8 clinical studies were included in our analysis. IDH inhibitors appear to have the best safety profile, with an overall grade 3/grade 4 adverse event rate of 9%. Response rates to IDH-mutant inhibitors were highest in nonenhancing gliomas (stable disease achieved in 55% of patients). In contrast, histone deacetylase inhibitors demonstrate a lower safety profile with single-study adverse events as high as 28%.
IDH inhibitors appear promising given their benign toxicity profile and ease of monitoring. Histone deacetylase inhibitors appear to have a narrow therapeutic index, as lower concentrations do not appear effective, while increased doses can produce severe immunosuppressive effects. Preliminary data suggest that epigenetic therapies are generally well tolerated and may control disease in certain patient groups, such as those with nonenhancing lesions.

A key event featured in the early stage of chronic gut inflammatory diseases is the disordered recruitment and excess accumulation of immune cells in the gut lamina propria. This process is followed by the over-secretion of pro-inflammatory factors and the prolonged overactive inflammatory responses. Growing evidence has suggested that gut inflammatory diseases may be mitigated by butyric acid (BA) or butyrate sodium (NaB). Laboratory studies show that BA and NaB can enhance gut innate immune function through G-protein-mediated signaling pathways while mitigating the overactive inflammatory responses by inhibiting histone deacetylase. The regulatory effects may occur in both epithelial enterocytes and the immune cells in the lamina propria. Prior to further clinical trials, comprehensive literature reviews and rigid examination concerning the underlying mechanism are necessary. To this end, we collected and reviewed 197 published reports regarding the mechanisms, bioactivities, and clinical effects of BA and NaB to modulate gut inflammatory diseases. Our review found insufficient evidence to guarantee the safety of clinical practice of BA and NaB, either by anal enema or oral administration of capsule or tablet. The safety of clinical use of BA and NaB should be further evaluated. Alternatively, dietary patterns rich in \"fruits, vegetables and beans\" may be an effective and safe approach to prevent gut inflammatory disease, which elevates gut microbiota-dependent production of BA. Our review provides a comprehensive reference to future clinical trials of BA and NaB to treat gut inflammatory diseases.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma composed of CD8+ cytotoxic T-cell that is primarily localized in the subcutaneous tissue. No standard treatments are currently available for SPTCL due to its rarity. Chemotherapy, radiotherapy, immunosuppressive agents, and hematopoietic stem cell transplantation (HSCT) have been used frequently, however, the effects of these treatment approaches remain controversial. In this report, we present an unusual case of SPTCL in a 47-year-old woman whose initial symptoms were atypical. The patient was started on etoposide, vincristine, cyclophosphamide, doxorubicin, and prednisone (EPOCH) chemotherapy once diagnosed. After two cycles of chemotherapy, her clinical symptoms were not significantly improved. Subsequently, histone deacetylase (HDAC) inhibitor chidamide was added to the chemotherapy from the third cycle. She recovered gradually and achieved complete remission (CR) after four cycles of chemotherapy combined with chidamide, followed by chidamide monotherapy for maintenance. More than 1 year after the therapy, she remained in CR. Our case illustrates, for the first time, chidamide can be an effective agent to induce long-term remission for rare SPTCL.

Peripheral T-cell lymphomas (PTCLs) are an aggressive and diverse group of lymphomas with a T-cell origin. Most patients progress following initial treatment and require salvage therapy. The burden of symptoms is high due to its extra-nodal presentation, high rate of advanced disease, and associated cytopenias combined with its predilection for an elderly population. The disease is generally incurable at relapse in the absence of transplantation and treatment is aimed at prolonging life and reducing disease-related symptoms. Belinostat is a histone deacetylate inhibitor that was granted accelerated approval by the US Food and Drug Administration on July 3, 2014, for the treatment of relapsed PTCL. Here, a systemic review was conducted to assess the safety and efficacy of belinostat. A safety analysis involved 512 patients with relapsed malignancies, and an efficacy analysis focused on patients with relapsed PTCL and included a total of 144 patients. Common adverse events were noted including fatigue (35%), nausea (42.8%), and vomiting (28.5%), but comparatively low rates of grade 3/4 hematologic toxicity overall (6.4%). Efficacy analysis demonstrated an overall response rate of 25.7% and complete responses of 10.4% with the majority of discontinuations occurring for lack of efficacy. Ultimately, these results demonstrate that belinostat has comparable efficacy to other agents used in this setting and is well tolerated in regard to hematologic events, but there is limited data on patient-reported outcomes, reduction in disease-related symptoms, or quality of life.

To compare the efficacy and safety between hypomethylating agent (HMA) alone and the combination of HMA and histone deacetylase inhibitor (HDACi) in myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
We performed a systematic review and meta-analysis of all available cohort studies regarding the comparison of HMA alone and in combination with HDACi for MDS and AML. Embase and Pubmed databases were searched for relevant studies. The overall hazard ratios for the HMA alone and HDACi combination were extracted. Heterogeneity among the included studies was evaluated by Cochrane\'s Q Test and I2 statistics. A random-effect model or a fixed-effect model was applied depending on the heterogeneity. Subgroup analysis was used to evaluate the source of heterogeneity.
Seven studies comprising 922 patients (458 patients treated with HMA alone and 464 with HMA and HDACi) were included in the analysis. Pooled data showed no significant differences in complete remission (CR) rates, hematologic improvement (HI), overall response rate (ORR), overall survival (OS), and toxicities between HMA alone treatment and HMA with HDACi regimens.
HDACi and HMA combination does not appear to be more effective and better tolerated than HMA alone. Future randomized controlled trials are needed to confirm its efficacy and safety.