Biologics : Targets & Therapy最新文献

{"title":"Non-Surgical Management of Recurrent Naso-Orbital Hemangiomas with Bevacizumab: A Case Report.","authors":"Shengyang Liu, Hui Zhao, Li Shi, Hongzhi Ji","doi":"10.2147/BTT.S482138","DOIUrl":"10.2147/BTT.S482138","url":null,"abstract":"<p><p>In this case report, we describe a 21-year-old man with recurrent hemangiomas in his left eye socket and nasal cavity. Traditional surgeries were unsuccessful, so we used Bevacizumab, a drug that inhibits blood vessel growth. This approach significantly reduced the tumor size and stopped frequent nosebleeds. Over two years, the tumor remained controlled without major side effects, suggesting Bevacizumab as a promising non-surgical treatment for recurrent hemangiomas.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of Long-Term Tocilizumab in a Cohort of Patients with Giant Cell Arteritis: An Italian Monocentric Retrospective Study.","authors":"Riccardo Terribili, Silvia Grazzini, Edoardo Conticini, Paolo Falsetti, Giovanni Biasi, Claudia Fabiani, Luca Cantarini, Bruno Frediani","doi":"10.2147/BTT.S470107","DOIUrl":"https://doi.org/10.2147/BTT.S470107","url":null,"abstract":"<p><strong>Objective: </strong>Tocilizumab (TCZ) is the only biologic drug approved for the treatment of giant cell arteritis (GCA), having clinical trials and real-life studies proved its efficacy and safety. However, the optimal duration of the treatment has yet to be determined, being its early interruption associated with an increased risk of relapse. Conversely, prolonged schemes of therapy may rise safety concerns. The aim of the study was to evaluate the incidence of adverse events (AEs) and remission/relapse rate in a cohort of GCA patients treated with TCZ and an accelerated steroid tapering scheme, followed for 24 months.</p><p><strong>Methods: </strong>We retrospectively included patients referring to our clinic from January 2019 to November 2021 who were diagnosed with GCA and started subcutaneous TCZ treatment (162 mg/week). They also received up to 62,5 mg of prednisone (PDN), tapered following an accelerated six-month scheme.</p><p><strong>Results: </strong>We collected 38 patients, with a mean age of 76,4 years, treated with TCZ for an average of 22,3 months. AEs occurred in 11 (29%) subjects, and only one serious AE was reported; 7 (18%) patients permanently discontinued TCZ. At the end of the follow-up, all the patients continuing treatment showed clinical remission, with a PDN dosage <5mg. We registered 3 (8%) minor relapses under TCZ, after an average of 15 months.</p><p><strong>Conclusion: </strong>Our data support the evidence of a safe and effective long-term use of TCZ in GCA patients, especially when combined with moderate GCs doses for the shortest possible duration.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Anticancer Potential of <i>Lactobacillus</i> Strains: Insights into Cytotoxicity and Apoptotic Mechanisms on HCT 115 Cancer Cells.","authors":"Luolin Wang, Zhenglei Xu, Aarti Bains, Nemat Ali, Zifang Shang, Abhinandan Patil, Sandip Patil","doi":"10.2147/BTT.S477602","DOIUrl":"10.2147/BTT.S477602","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to systematically assess the anticancer potential of distinct <i>Lactobacillus</i> strains on Human Colorectal Tumor (HCT) 115 cancer cells, with a primary focus on the apoptotic mechanisms involved. <i>Lactobacillus</i> strains were isolated from sheep milk and underwent a meticulous microbial isolation process. Previous research indicates that certain probiotic bacteria, including Lactobacillus species, may exhibit anticancer properties through mechanisms such as apoptosis induction. However, there is limited understanding of how different <i>Lactobacillus</i> strains exert these effects on cancer cells and the underlying molecular pathways involved.</p><p><strong>Methods: </strong>Cytotoxicity was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and exposure durations of <i>Lactobacillus</i> cell-free lyophilized filtrates. Additional apoptotic features were characterized using 4.6-diamidino-2-phenylindole (DAPI) analysis for nuclear fragmentation and Annexin V/PI analysis for apoptosis quantification. Genetic analysis explored the modulation of apoptotic proteins (Bax and Bcl₂) in response to <i>Lactobacillus</i> treatment. Whole-genome sequencing (WGS) was performed to understand the genetic makeup of the <i>Lactobacillus</i> strains used in the study.</p><p><strong>Results: </strong>The study demonstrated a significant reduction in HCT 115 cell viability, particularly with <i>L. plantarum</i>, as evidenced by Sulforhodamine B (SRB) and MTT assays. DAPI analysis revealed nuclear fragmentation, emphasizing an apoptotic cell death mechanism. Annexin V/PI analysis supported this, showing a higher percentage of early and late apoptosis in <i>L. plantarum</i>-treated cells. Genetic analysis uncovered up-regulation of pro-apoptotic protein Bax and down-regulation of anti-apoptotic protein Bcl₂ in response to <i>Lactobacillus</i> treatment. WGS study revealed a strain reported to NCBI PRJNA439183.</p><p><strong>Discussion: </strong><i>L. plantarum</i> emerged as a potent antiproliferative agent against HCT 115 cancer cells, inducing apoptosis through intricate molecular mechanisms. This study underscores the scientific basis for <i>L. plantarum's</i> potential role in cancer therapeutics, highlighting its impact on antiproliferation, adhesion, and gene-protein regulation. Further research is warranted to elucidate the specific molecular pathways involved and to evaluate the therapeutic potential of <i>L. plantarum</i> in preclinical and clinical settings.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11453158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing AREG Enhances Sensitivity to Irradiation by Suppressing the PI3K/AKT Signaling Pathway in Colorectal Cancer Cells.","authors":"Wenbing Zhang, Wenjuan Zhang, Chenling Tang, Yan Hu, Ke Yi, Xiaohui Xu, Zhihua Chen","doi":"10.2147/BTT.S480361","DOIUrl":"10.2147/BTT.S480361","url":null,"abstract":"<p><strong>Background: </strong>It has been established that Spalt-Like Transcription Factor 4 (SALL4) promotes Colorectal Cancer (CRC) cell proliferation. Furthermore, Amphiregulin (AREG) is crucially involved in cancer cell proliferation and therapeutic resistance regulation. In this regard, this study aimed to establish whether SALL4 affects the radiosensitization of CRC cells via AREG expression regulation.</p><p><strong>Methods: </strong>Transcriptome sequencing and the Human Transcription Factor Database (HumanTFDB) were used to identify the potential SALL4 targets. The dual-luciferase reporter analysis was used to confirm the SALL4-induced AREG activation. Western Blot (WB) and Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) assays were used to examine the effect of X-ray irradiation on SALL4 and AREG expression. The AREG-KD (Knockdown) stable cell lines were created through lentiviral infection. Cell proliferation was tracked using Cell Counting Kit 8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU)-incorporation assays. Cell cycle and apoptosis were examined through flow cytometry. The cells were exposed to a controlled X-ray radiation dose (6 Gy) for imaging purposes.</p><p><strong>Results: </strong>SALL4 could bound to the AREG promoter, enhancing AREG expression. Furthermore, irradiation upregulated SALL4 and AREG in CRC cells. Additionally, AREG knockdown in CRC cells led to reduced DNA replication efficiency, suppressed cell proliferation, increased DNA damage, and enhanced G1 phase arrest and apoptosis following irradiation. On the other hand, AREG overexpression reversed the inhibitory effects of SALL4 downregulation on AREG expression.</p><p><strong>Conclusion: </strong>In CRC cells, SALL4 downregulation suppressed AREG expression, regulating CRC cell radiosensitivity via the PI3K-AKT pathway, thus presenting a potential therapeutic pathway for CRC treatment using Radiotherapy (RT).</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary Investigation and Therapeutic Efficacy Determination of a Novel Anti-IL-17A Antibody, Indikizumab.","authors":"Ashok Kumar Patra, Shreenath Nayak, Anandita Moharana, Purusottam Ojha, Sanjeet Kumar Das, Jabed Akhtar, Bishwaranjan Giri, Sujay Singh","doi":"10.2147/BTT.S477752","DOIUrl":"https://doi.org/10.2147/BTT.S477752","url":null,"abstract":"<p><strong>Purpose: </strong>The study aimed to develop and characterize Indikizumab, a novel humanized anti-IL-17A monoclonal antibody (mAb), for potential therapeutic use in inflammatory indications such as psoriasis, psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis.</p><p><strong>Methods: </strong>The research involved the purification of IL-17 isoforms, epitope mapping, affinity ranking, and comparative binding assessment of anti-IL-17 antibodies. The study also included cell-based neutralization assays and in vivo studies using mouse models to evaluate the efficacy of Indikizumab.</p><p><strong>Results: </strong>Indikizumab demonstrated a high binding affinity (K_D=27.2 pM) and specificity for IL-17A, with comparable potency to Secukinumab. In cell-based neutralization assays, Indikizumab effectively neutralized the effects of IL-17A and demonstrated a statistically significant reduction in plasma KC (Keratinocyte) levels in a mouse model. In imiquimod-induced psoriasis mouse model, Indikizumab showed potential in reducing the psoriasis index.</p><p><strong>Conclusion: </strong>Indikizumab represents a promising therapeutic option for inflammatory indications with its high binding affinity, specificity for IL-17A, and effectiveness in neutralizing IL-17A effects in vivo.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Herbal Therapies for Cancer Treatment: A Review of Phytotherapeutic Efficacy.","authors":"Andrej Jenča, David K Mills, Hadis Ghasemi, Elham Saberian, Andrej Jenča, Amir Mohammad Karimi Forood, Adriána Petrášová, Janka Jenčová, Zeinab Jabbari Velisdeh, Hadi Zare-Zardini, Meysam Ebrahimifar","doi":"10.2147/BTT.S484068","DOIUrl":"https://doi.org/10.2147/BTT.S484068","url":null,"abstract":"<p><p>Natural products have proven to be promising anti-cancer agents due to their diverse chemical structures and bioactivity. This review examines their central role in cancer treatment, focusing on their mechanisms of action and therapeutic benefits. Medicinal plants contain bioactive compounds, such as flavonoids, alkaloids, terpenoids and polyphenols, which exhibit various anticancer properties. These compounds induce apoptosis, inhibit cell proliferation and cell cycle progression, interfere with microtubule formation, act on topoisomerase targets, inhibit angiogenesis, modulate key signaling pathways, improve the tumor microenvironment, reverse drug resistance and activate immune cells. Herbal anti-cancer drugs offer therapeutic advantages, particularly selective toxicity against cancer cells, reducing the adverse side effects associated with conventional chemotherapy. Recent studies and clinical trials highlight the benefits of herbal medicines in alleviating side effects, improving tolerance to chemotherapy and the occurrence of synergistic effects with conventional treatments. For example, the herbal medicine SH003 was found to be safe and potentially effective in the treatment of solid cancers, while Fucoidan showed anti-inflammatory properties that are beneficial for patients with advanced cancer. The current research landscape on herbal anticancer agents is extensive. Numerous studies and clinical trials are investigating their efficacy, safety and mechanisms of action in various cancers such as lung, prostate, breast and hepatocellular carcinoma. Promising developments include the polypharmacological approach, combination therapies, immunomodulation and the improvement of quality of life. However, there are still challenges in the development and use of natural products as anti-cancer drugs, such as the need for further research into their mechanisms of action, possible drug interactions and optimal dosage. Standardizing herbal extracts, improving bioavailability and delivery, and overcoming regulatory and acceptance hurdles are critical issues that need to be addressed. Nonetheless, the promising anticancer effects and therapeutic benefits of natural products warrant further investigation and development. Multidisciplinary collaboration is essential to advance herbal cancer therapy and integrate these agents into mainstream cancer treatment.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11401522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aspergillus Species from the Sabkha Marsh: Potential Antimicrobial and Anticancer Agents Revealed Through Molecular and Pharmacological Analysis.","authors":"Bayan H Sajer, Wafa A Alshehri, Sahar S Alghamdi, Rasha S Suliman, Alhanouf Albejad, Haifa Hakmi","doi":"10.2147/BTT.S472491","DOIUrl":"10.2147/BTT.S472491","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to investigate the fungal growth and diversity in the Sabkha marsh. The anti-bacterial properties of the isolated fungi were assessed using an agar disk diffusion assay, and the crude extracts were tested for their anticancer activities. Liquid chromatography-mass spectrometry was employed to identify the active compounds of the fungal secondary metabolites. In-silico studies were conducted to predict the toxicity, pharmacokinetic properties, and safety profiles of the identified compounds.</p><p><strong>Results: </strong>The analysis revealed that the isolated fungi belonged to the Aspergillus species, specifically <i>Aspergillus flavus</i> and <i>Aspergillus niger</i>. The crude extract of <i>A. flavus</i> exhibited significant anticancer activity against various cancer cell lines, while the antifungal activities against pathogenic bacteria varied between the two fungi. Liquid chromatography-mass spectrometry analysis identified several compounds in the fungal isolates. In <i>Aspergillus flavus</i>, the compounds included Aflavinine, Dihydro-24-hydroxyaflavinine, Phomaligin A, Hydroxysydonic acid, Gregatin B, Pulvinulin A, Chrysogine, Aspergillic acid, Aflatoxin B1, and Aflatoxin G1. In <i>Aspergillus niger</i>, the compounds identified were atromentin, fonsecin B, firalenone, rubrofusarin, aurasperone E, aurasperone D, aurasperone C, nigerone, and αβ-dehydrocurvularin.</p><p><strong>Conclusion: </strong>This study demonstrated promising fungal growth and diversity in the Sabkha marsh, with Aspergillus species being the most prevalent. The fungal crude extract showed anticancer activities against various cancer cell lines, while the antifungal activities against pathogenic bacteria varied between the two fungi. Future research should focus on investigating the antimicrobial activities of these fungi against multidrug-resistant bacteria and exploring the genetic changes in bacteria and cancer cells treated with these fungal extracts. Additionally, it is important to test the anticancer activity of the active compounds separately to determine which one is the active agent against cancer cells. This information can be used in drug development trials.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Underlying Molecular Mechanisms of Yunke on Bone Metastases from Prostate Cancer.","authors":"Simin Liu, Zhiyuan Tian, Taiming Zhang, Jirong Zhang, Yanlei Huo, Chao Ma","doi":"10.2147/BTT.S457188","DOIUrl":"10.2147/BTT.S457188","url":null,"abstract":"<p><strong>Objective: </strong>To explore analgesic effect and bone repair mechanism of non-radioactive technetium-99 conjugated with methylene diphosphonate (⁹⁹Tc-MDP, brand name, Yunke) on bone metastases (BM).</p><p><strong>Procedures: </strong>In vivo experiment, mouse BM models of prostate cancer RM-1 cell were constructed and divided into Control, Yunke, ⁹⁹Tc+SnCl₂ and MDP groups based on medicine composition. Tumor specimens were inspected for size, X-ray, microCT and histopathology. In vitro experiment, with Cell Counting Kit-8 (CCK8), scratch, clone, apoptosis, Polymerase Chain Reaction (PCR) and Western Blot experiments, effects of Yunke on RM-1 cells and osteoclast-related cells were observed.</p><p><strong>Results: </strong>In vivo experiment, there was no difference in tumor size between Yunke and control group. Contrasted with control group, in Yunke group, trabecular spacing (Tb.Sp) of tumor bone was lower, bone volume/total volume (BV/TV) on marrow cavity and bone cortex were higher. Tunnel staining showed that positive rate of apoptosis in Yunke group was higher than that in control group. Ki67 staining showed that Yunke could not inhibit proliferation of tumor cells. In vitro experiment, CCK8 and scratch experiments showed that Yunke neither can inhibit proliferation nor can inhibit migration of RM-1 cells. High concentration of Yunke promoted late apoptosis of RM-1 cells. Yunke could inhibit BMM cell proliferation, differentiation of osteoclasts, and osteoclast-related transcription factors. Yunke displayed different degrees of inhibitory effects on MAPKs signaling pathway during osteoclast differentiation. It had obvious inhibitory effects on osteoclast-related transcription factors, such as cFOS, NFATC1, ACP-5, CTSK, D2 and MMP-9, the strongest inhibitory effects were observed with ACP-5, CTSK and D2. Yunke also displayed different degrees of inhibitory effects on protein activities of JNK, pERK, ERK and pP38.</p><p><strong>Conclusion: </strong>Yunke cannot inhibit the proliferation and migration of RM-1 cells, so we think it is not recommended for the treatment of primary tumors and prevention of occurrence of tumors metastatic to bones. The mechanism of therapeutic effect of Yunke on BM by inhibiting proliferation of BMM, inhibiting MAPKs signal transduction and activation of transcription factors during differentiation process of BMM-derived osteoclasts, inhibiting number and size of osteoclasts, inhibiting bone resorption and protecting bone destruction through enhancing bone hardness and bone mass. Thereby, we believe that Yunke is more suitable for promoting the repair induced by BMs, delaying its progression and reducing the occurrence of SREs.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11278808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STAT5B Suppresses Ferroptosis by Promoting DCAF13 Transcription to Regulate p53/xCT Pathway to Promote Mantle Cell Lymphoma Progression.","authors":"Wen Jun Zhang, Chong Ling Hu, Bing Ling Guo, Xi Ping Liang, Chao Yu Wang, Tao Yang","doi":"10.2147/BTT.S461287","DOIUrl":"10.2147/BTT.S461287","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this study was to analyze the mechanism by which STAT5B inhibits ferroptosis in mantle cell lymphoma (MCL) by promoting DCAF13 transcriptional regulation of p53/xCT pathway.</p><p><strong>Methods: </strong>The correlations between STAT5B, DCAF13 and ferroptosis in MCL were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA, http://gepia.cancer-pku.cn/index.html). The expression levels and pairwise correlations of STAT5B, DCAF13, p53 and xCT in MCL patients were detected, respectively. STAT5B was silenced to confirm their criticality in MCL ferroptosis. the effects of blocking necrosis, apoptosis and ferroptosis on the anti-MCL effects of STAT5B were examined. Cells with STAT5B overexpression and/or DCAF13 silencing were constructed to confirm the involvement of DCAF13 in the STAT5B-regulated p53/xCT pathway. The regulation of p53 ubiquitination was confirmed by DCAF13 overexpression and MG132. The effects of silencing DCAF13 and MG132 on STAT5B overexpression on MCL was clarified by a tumor-bearing nude mouse model.</p><p><strong>Results: </strong>DCAF13 was overexpressed in MCL and positively correlated with STAT5B, negatively correlated with p53, and positively correlated with xCT. Inhibition of ferroptosis alleviated the inhibitory effects of siSTAT5B on MCL, while inhibition of necrosis and apoptosis had few effects. Silencing of DCAF13 led to the blocking of STAT5B regulation of p53/xCT and ferroptosis. The changes in DCAF13 and the addition of MG132 did not have statistically significant effects on p53 mRNA. Elevation of DCAF13 resulted in downregulation of p53 protein levels, and this inhibition was reversed by MG132. In animal models, the promotion of MCL and the inhibition of ferroptosis by STAT5B. Silencing of DCAF13 blocked STAT5B inhibition of p53 and induction of xCT, GPX4, and GSH.</p><p><strong>Conclusion: </strong>STAT5B suppresses ferroptosis by promoting DCAF13 transcription to regulate p53/xCT pathway to promote MCL progression.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzymatic Routes for Chiral Amine Synthesis: Protein Engineering and Process Optimization.","authors":"Sayali Shantaram Vikhrankar, Seema Satbhai, Priyanka Kulkarni, Ranjit Ranbhor, Vibin Ramakrishnan, Prashant Kodgire","doi":"10.2147/BTT.S446712","DOIUrl":"10.2147/BTT.S446712","url":null,"abstract":"<p><p>Chiral amines are essential motifs in pharmaceuticals, agrochemicals, and specialty chemicals. While traditional chemical routes to chiral amines often lack stereoselectivity and require harsh conditions, biocatalytic methods using engineered enzymes can offer high efficiency and selectivity under sustainable conditions. This review discusses recent advances in protein engineering of transaminases, oxidases, and other enzymes to improve catalytic performance. Strategies such as directed evolution, immobilization, and computational redesign have expanded substrate scope and enhanced efficiency. Furthermore, process optimization guided by techno-economic assessments has been crucial for establishing viable biomanufacturing routes. Combining state-of-the-art enzyme engineering with multifaceted process development will enable scalable, economical enzymatic synthesis of diverse chiral amine targets.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}