Biologics : Targets & Therapy最新文献

{"title":"Gene Expression, Morphology, and Electrophysiology During the Dynamic Development of Human Induced Pluripotent Stem Cell-Derived Atrial- and Ventricular-Like Cardiomyocytes [Letter].","authors":"Mayang Wulandari, Amal Prihatono, Achmad Jaelani Rusdi","doi":"10.2147/BTT.S480180","DOIUrl":"10.2147/BTT.S480180","url":null,"abstract":"","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"18 ","pages":"145-146"},"PeriodicalIF":5.3,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11162613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295548","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":"Response to \"Lncrna GAS5 Modulates the Progression of Glioma Through Repressing miR-135b-5p and Upregulating APC\" [Letter].","authors":"Chanif Mahdi, Mayang Wulandari, Retno Dewi Prisusanti","doi":"10.2147/BTT.S479606","DOIUrl":"10.2147/BTT.S479606","url":null,"abstract":"","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"18 ","pages":"143-144"},"PeriodicalIF":4.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11162621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295549","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":"Gene Expression, Morphology, and Electrophysiology During the Dynamic Development of Human Induced Pluripotent Stem Cell-Derived Atrial- and Ventricular-Like Cardiomyocytes.","authors":"Yafei Zhou, Rui Zhou, Wenjun Huang, Jie Wang, Congshan Jiang, Anmao Li, Christopher L H Huang, Yanmin Zhang","doi":"10.2147/BTT.S448054","DOIUrl":"10.2147/BTT.S448054","url":null,"abstract":"<p><strong>Background and objectives: </strong>Gene expression, morphology, and electrophysiological combination are essential for assessing the dynamic development of human induced pluripotent stem cell-derived atrial- and ventricular-like cardiomyocytes (iPS-AM and iPS-VM, respectively).</p><p><strong>Methods: </strong>For iPS-AM/VM differentiation, we performed the small molecule-based temporal modulation of the retinoic acid and bone morphogenetic protein signaling pathways. We investigated the gene expression and morphology using immunofluorescence, quantitative real-time polymerase chain reaction, flow cytometry, and transmission electron microscopy as well as registered electrophysiological functions using a whole-cell patch clamp on days 20, 30, and 60 post-differentiations.</p><p><strong>Results: </strong>Pan-cardiomyocyte marker, including troponin T2 (<i>TNNT2</i>) and alpha-actinin-2 (<i>ACTN2</i>), expressions increased both in iPS-AMs and iPS-VMs. Similarly, the mRNA expression of both iPS-AM-specific markers, ie, natriuretic peptide A (<i>NPPA</i>), myosin light chain 7 (<i>MYL7</i>), and K+ channel Kir3.4 (<i>KCNJ5</i>), and iPS-VM-specific markers, ie, gap junction α-1 (<i>GJA1</i>), myosin light chain 2 (<i>MYL2</i>), and alpha-1-subunit of a voltage-dependent L-type calcium channel (<i>CACNA1C</i>), increased from 0 to 20 days, and then decreased from 30 to 60 days. Concerning morphology, cardiac troponin-T (cTnT) arrangement was progressively organized and developed from a disorderly myofibrillar distribution to an organized sarcomere pattern both in iPS-AMs and iPS-VMs. Mitochondrial numbers gradually increased and those of lipid droplets decreased during dynamic development. Regarding physiological function, the resting and action potential amplitudes remained statistically indifferent in both cell types, and the action potential duration was prolonged during the development.</p><p><strong>Conclusion: </strong>IPS-AMs/VMs displayed dynamic development concerning their gene expression, morphology, and electrophysiological function. The discoveries of this study could provide novel insights into heart development and encourage further research.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"18 ","pages":"115-127"},"PeriodicalIF":4.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920268","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":"Successful Fistula Closure After Treatment with Colostomy and Infliximab in a Patient with Ulcerative Colitis Complicated by Rectovaginal Fistula.","authors":"Sota Katsube, Satohiro Matsumoto, Masahiro Misawa, Nao Kakizawa, Ryo Hashimoto, Taku Mizutani, Keita Matsumoto, Shuhei Yoshikawa, Hirosato Mashima","doi":"10.2147/BTT.S457300","DOIUrl":"10.2147/BTT.S457300","url":null,"abstract":"<p><p>The patient was a 50-year-old Japanese woman who was diagnosed with total-colitis-type ulcerative colitis (UC) at the age of 26 years. She was treated with mesalazine and azathioprine, and her disease activity was well controlled. At the age of 50 years, the patient was experiencing fever, abdominal pain, diarrhea, bloody stool, and anal pain, which led to a diagnosis of a relapse of UC. Although steroid therapy was administered and tended to improve her symptoms, fecaloid vaginal discharge occurred, and rectovaginal fistula (RVF) was confirmed. Colostomy was performed, and infliximab was initiated as maintenance therapy for UC. All symptoms improved, and RVF closure was confirmed 6 months after the initiation of infliximab. To date, she has been free from relapse of UC. There have been only a few reports of UC complicated by RVF, and this condition is often difficult to treat. To the best of our knowledge, no other case of UC complicated by RVF in which the fistula was closed after treatment with colostomy and infliximab has been previously reported; thus, our report of the present case is valuable to the literature.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"18 ","pages":"107-113"},"PeriodicalIF":4.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11086393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911002","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":"<i>TNFSF13B</i> rs9514828 C>T Polymorphism is Associated with Incidence of Atherosclerosis and Therapeutic Outcomes in Patients with Systemic Lupus Erythematosus.","authors":"Desi Reski Fajar, Tina Rostinawati, Laniyati Hamijoyo, Edhyana Sahiratmadja, Riezki Amalia, Melisa Intan Barliana","doi":"10.2147/BTT.S452792","DOIUrl":"10.2147/BTT.S452792","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is a complex autoimmune disease with numerous clinical manifestations. Organ involvement can aggravate patients with SLE and cause comorbidities such as atherosclerosis. Recently, the <i>TNFSF13B</i> gene has been found to be linked with SLE events. This study aimed to analyze the association between single nucleotide polymorphisms of the <i>TNFSF13B</i> rs9514828 with incidence of atherosclerosis and therapeutic outcomes in patients with SLE.</p><p><strong>Patients and methods: </strong>This case-control study included 84 SLE patients, of whom 21 patients with SLE with atherosclerosis and 63 patients with SLE without atherosclerosis. Using enzyme-linked immunosorbent assay method, interleukin-6 and interferon gamma levels were quantified. The <i>TNFSF13B</i> gene polymorphism was evaluated using polymerase chain reaction followed by sequencing. The lupus low disease activity state (LLDAS) criteria were used to measure the therapeutic outcomes. Statistical analysis was conducted using binary logistic regression.</p><p><strong>Results: </strong>The genetic variations of <i>TNFSF13B</i> rs9514828 were CC = 35, CT = 41, and TT = 8. There was an association between <i>TNFSF13B</i> rs9514828 C>T polymorphism in patients with SLE with and without atherosclerosis (p = 0.03; odds ratio (OR) 4.72, 95% confidence interval [CI] 1.22-18.37). Furthermore, the <i>TNFSF13B</i> rs9514828 C>T polymorphism had association with the therapeutic outcomes of patients with SLE who manifested with LLDAS (p = 0.00; OR 7.58, 95% CI 2.61-21.99).</p><p><strong>Conclusion: </strong>The association of <i>TNFSF13B</i> rs9514828 C>T polymorphism and incidence of atherosclerosis as well as the therapeutic outcomes in patients with SLE indicate the potential utility of the gene variation as screening tool to employ personalized medicine to undertake preventive measures in order to prevent atherosclerosis and to predict a poor prognosis in SLE patient.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"18 ","pages":"95-106"},"PeriodicalIF":4.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875854","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":"MDMX in Cancer: A Partner of p53 and a p53-Independent Effector.","authors":"Wu Lin, Yuxiang Yan, Qingling Huang, Dali Zheng","doi":"10.2147/BTT.S436629","DOIUrl":"10.2147/BTT.S436629","url":null,"abstract":"<p><p>The p53 tumor suppressor protein plays an important role in physiological and pathological processes. MDM2 and its homolog MDMX are the most important negative regulators of p53. Many studies have shown that MDMX promotes the growth of cancer cells by influencing the regulation of the downstream target gene of tumor suppressor p53. Studies have found that inhibiting the MDMX-p53 interaction can effectively restore the tumor suppressor activity of p53. MDMX has growth-promoting activities without p53 or in the presence of mutant p53. Therefore, it is extremely important to study the function of MDMX in tumorigenesis, progression and prognosis. This article mainly reviews the current research progress and mechanism on MDMX function, summarizes known MDMX inhibitors and provides new ideas for the development of more specific and effective MDMX inhibitors for cancer treatment.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"18 ","pages":"61-78"},"PeriodicalIF":4.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10839028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691170","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":"Recent Advancements in Reducing the Off-Target Effect of CRISPR-Cas9 Genome Editing.","authors":"Misganaw Asmamaw Mengstie, Muluken Teshome Azezew, Tadesse Asmamaw Dejenie, Assefa Agegnehu Teshome, Fitalew Tadele Admasu, Awgichew Behaile Teklemariam, Anemut Tilahun Mulu, Melaku Mekonnen Agidew, Dagnew Getnet Adugna, Habtamu Geremew, Endeshaw Chekol Abebe","doi":"10.2147/BTT.S429411","DOIUrl":"10.2147/BTT.S429411","url":null,"abstract":"<p><p>The CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)) and the associated protein (Cas9) system, a young but well-studied genome-editing tool, holds plausible solutions to a wide range of genetic disorders. The single-guide RNA (sgRNA) with a 20-base user-defined spacer sequence and the Cas9 endonuclease form the core of the CRISPR-Cas9 system. This sgRNA can direct the Cas9 nuclease to any genomic region that includes a protospacer adjacent motif (PAM) just downstream and matches the spacer sequence. The current challenge in the clinical applications of CRISPR-Cas9 genome-editing technology is the potential off-target effects that can cause DNA cleavage at the incorrect sites. Off-target genome editing confuses and diminishes the therapeutic potential of CRISPR-Cas9 in addition to potentially casting doubt on scientific findings regarding the activities of genes. In this review, we summarize the recent technological advancements in reducing the off-target effect of CRISPR-Cas9 genome editing.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"18 ","pages":"21-28"},"PeriodicalIF":5.3,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519664","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":"Effect of N-Acetylcysteine on Cisplatin Toxicity: A Review of the Literature.","authors":"Angeles Citlali Zavala-Valencia, Liliana Velasco-Hidalgo, Armando Martínez-Avalos, Manuel Castillejos-López, Luz-María Torres-Espíndola","doi":"10.2147/BTT.S438150","DOIUrl":"10.2147/BTT.S438150","url":null,"abstract":"<p><p>N-acetylcysteine (NAC) is a membrane-permeable cysteine precursor capable of enhancing the intracellular cysteine pool, enhancing cellular glutathione (GSH) synthesis, and thus potentiating the endogenous antioxidant mechanism. Late administration of NAC after cisplatin has been shown in different in vivo studies to reduce the side effects caused by various toxicities at different levels without affecting the antitumor efficacy of platinum, improving total and enzymatic antioxidant capacity and decreasing oxidative stress markers. These characteristics provide NAC with a rationale as a potentially effective chemo protectant in cisplatin-based therapeutic cycles. NAC represents a potential candidate as a chemoprotective agent to decrease toxicities secondary to cisplatin treatment. It suggests that it could be used in clinical trials, whereby the effective dose, timing, and route should be adjusted to optimize chemoprotection. This review provides an overview of the effect of NAC on cisplatin toxicity, a drug widely used in the clinic in adults and children.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"18 ","pages":"7-19"},"PeriodicalIF":4.0,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10799624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511544","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":"Successful Response to Golimumab in a Case of Relapsing Polychondritis Overlapping with Ulcerative Colitis.","authors":"Shu Kojima, Satohiro Matsumoto, Yudai Koito, Takaya Miura, Masanari Sekine, Takeshi Uehara, Takeharu Asano, Yasuhiro Yamaguchi, Hirosato Mashima","doi":"10.2147/BTT.S436301","DOIUrl":"10.2147/BTT.S436301","url":null,"abstract":"<p><p>A 51-year-old Japanese man was diagnosed with left-sided ulcerative colitis (UC) at age 41. He was treated with mesalazine and azathioprine and maintained remission. At age 51, the patient developed bloody stools, abdominal pain, scleritis, arthritis, cough, bloody sputum, and pericardial effusion. Considering that pericardial effusion is an atypical extraintestinal complication of UC, and the patient met the diagnostic criteria for relapsing polychondritis (RP), a diagnosis of RP complicating a relapse of UC was made. Steroid therapy was administered, and both diseases improved. Golimumab, an anti-tumor necrosis factor-α inhibitor, was introduced as maintenance therapy for UC. All symptoms, including pericardial effusion, improved. Subsequently, no relapse of UC or RP was observed. As only a few cases of RP overlapping with UC have been reported and no treatment protocol has been established, we considered this case valuable and worthy of publication.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"18 ","pages":"1-6"},"PeriodicalIF":4.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485113","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":"Hypoxia Inducible Factor-1α Through ROS/NLRP3 Pathway Regulates the Mechanism of Acute Ischemic Stroke Microglia Scorching Mechanism.","authors":"Xin Ma, Junxia Jiao, Mayila Aierken, Hong Sun, Li Chen","doi":"10.2147/BTT.S444714","DOIUrl":"https://doi.org/10.2147/BTT.S444714","url":null,"abstract":"<p><strong>Purpose: </strong>In vitro experiments explored how the hypoxia-induced factor-1α (HIF-1α) regulates the regulation of pyroptosis in microglial cells (BV 2) in acute ischemic stroke through ROS/NLRP3 pathway.</p><p><strong>Methods: </strong>The microglia acute phase oxygen-glucose deprivation/reoxygenation (OGD/R) was established, CCK-8 was applied to determine the optimal timing of intervention modeling. HIF-1α was overexpressed with stabilizer GF-4592 and HIF-1α small molecule interfering RNA (HIF-1α-siRNA), which was divided into group A (blank group), group B (OGD/R model group), group C (model+FG-4592 intervention group), group D (model+siRNA negative control group) and group E (model+HIF-1α-siRNA group). Cell proliferation of different groups was measured by CCK-8 assay. Pyroptosis and intracellular ROS levels were measured by flow cell technology. IL-18, IL-1β levels were measured by ELISA. HIF-1α, GSDMD-D, GSDMD-N, clean-Caspase-1 and NLRP3 protein expression levels were measured by Western blot. On the above experiments, ROS and NLRP3 response experiments were performed to explore how HIF-1α regulates pyroptosis through ROS/NLRP3 pathway.</p><p><strong>Results: </strong>Hypoxia for 6 h then reoxygenation for 12 h was the optimal intervention time. Compared with groups B and D, cell proliferation in group C was significantly enhanced, pyroptosis, intracellular levels of ROS, IL-18, IL-1β and the expression of GSDMD-D, GSDMD-N, clean-Caspase-1, and NLRP3 proteins were significantly decreased in group C (<i>P</i> < 0.05). However, in group E, the performance of these test indicators were exactly the opposite, and the difference was statistically significant (<i>P</i> < 0.05). Through ROS and NLRP3 response experiments, it was found that HIF-1α Inhibition of Pyroptosis by inhibiting ROS/NLRP3 pathway.</p><p><strong>Conclusion: </strong>Overexpression of HIF-1α factor can inhibit microglia pyroptosis. HIF-1α factor has an inhibitory effect on the ROS/NLRP 3 pathway, which can inhibit the pyroptotic process in microglia.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"167-180"},"PeriodicalIF":4.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10748736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032159","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}