Advanced pharmaceutical bulletin最新文献

{"title":"The Art of Bioimmunogenomics (BIGs) 5.0 in CAR-T Cell Therapy for Lymphoma Management","authors":"Dito Anurogo, Dewi Luthfiana, Nuralfin Anripa, Apriliani Ismi Fauziah, Maratu Soleha, Laila Rahmah, Hana Ratnawati, T. Wargasetia, Sari Eka Pratiwi, Riswal Nafi Siregar, Ratis Nour Sholichah, Yu Hsiang Chang, Taruna Ikrar, Jiantai Timothy Qiu, Muhammad Sobri Maulana","doi":"10.34172/apb.2024.034","DOIUrl":"https://doi.org/10.34172/apb.2024.034","url":null,"abstract":"Purpose: Lymphoma, the most predominant neoplastic disorder, is divided into Hodgkin and Non-Hodgkin Lymphoma classifications. Immunotherapeutic modalities have emerged as essential methodologies in combating lymphoid malignancies. Chimeric Antigen Receptor (CAR) T cells exhibit promising responses in chemotherapy-resistant B-cell non-Hodgkin lymphoma cases. Methods: This comprehensive review delineates the advancement of CAR-T cell therapy as an immunotherapeutic instrument, the selection of lymphoma antigens for CAR-T cell targeting, and the conceptualization, synthesis, and deployment of CAR-T cells. Furthermore, it encompasses the advantages and disadvantages of CAR-T cell therapy and the prospective horizons of CAR-T cells from a computational research perspective. In order to improve the design and functionality of artificial CARs, there is a need for TCR recognition investigation, followed by the implementation of a quality surveillance methodology. Results: Various lymphoma antigens are amenable to CAR-T cell targeting, such as CD19, CD20, CD22, CD30, the kappa light chain, and ROR1. A notable merit of CAR-T cell therapy is the augmentation of the immune system's capacity to generate tumoricidal activity in patients exhibiting chemotherapy-resistant lymphoma. Nevertheless, it also introduces manufacturing impediments that are laborious, technologically demanding, and financially burdensome. Physical, physicochemical, and physiological limitations further exacerbate the challenge of treating solid neoplasms with CAR-T cells. Conclusion: While the efficacy and safety of CAR-T cell immunotherapy remain subjects of fervent investigation, the promise of this cutting-edge technology offers valuable insights for the future evolution of lymphoma treatment management approaches. Moreover, CAR-T cell therapies potentially benefit patients, motivating regulatory bodies to foster international collaboration.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140255159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming Breast Cancer Drug Resistance: A Novel Approach Using siRNA-Mediated P-glycoprotein Downregulation to Enhance Vinorelbine Efficacy","authors":"Zahra Abbasfard, Abbas Behzad Behbahani, Banafsheh Rastegari, Siroos Naeimi, M. Moghanibashi, Fatemeh Safari","doi":"10.34172/apb.2024.030","DOIUrl":"https://doi.org/10.34172/apb.2024.030","url":null,"abstract":"Purpose: Cancer, the second leading cause of mortality worldwide, represents a global health challenge, primarily due to drug resistance. Vinorelbine (Vino) is a chemotherapeutic agent that disrupts cancer cell growth by targeting microtubules and inducing apoptosis. However, drug resistance remains a formidable obstacle. This resistance is caused by various factors including genetic mutations, drug efflux mechanisms, and DNA repair systems. Resolution of this challenge requires an innovative approach. This study investigated the potential of small interfering RNA (siRNA) to target and downregulate a vinorelbine-resistant MCF-7/ADR breast cancer cell line. Methods: Cells were cultured in Dulbecco’s modified Eagle’s medium 10% fetal bovine serum/penicillin/streptomycin. An siRNA targeting ABCB1 was designed and synthesized, and the cells were transfected with siRNA at final concentrations of 10, 20, and 30 nM. The3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess cell viability. ABCB1 mRNA expression levels were determined by real-time PCR. Results: MCF-7 cells exhibited a higher sensitivity to vinorelbine than MCF-7/ADR cells. MCF-7/ADR cells exhibited resistance to vinorelbine at concentrations, 12.50 and 25.00 μM. Treatment with siRNA significantly reduced ABCB1 expression by 2.93-fold (p = 0.0001). Similarly, co-treatment with siRNA and vinorelbine produced a substantial 2.89-fold decrease in ABCB1 gene expression in MCF-7 cells compared to that in MCF-7/ADR cells (P =0.0001). Conclusion: The results of the present study indicate that the concurrent use of siRNA and vinorelbine holds substantial promise as a therapeutic approach to overcome ABCB1-mediated multidrug resistance (MDR) in breast cancer. It is necessary to conduct comprehensive clinical trials to determine the true effectiveness of this combination therapy.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140256150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcending traditional treatment: the therapeutical potential of nanovesicles for transdermal baclofen delivery in repeated traumatic brain injury","authors":"N. M. Sheta, Amira Ahmed El-Gazzar, G. Ragab, Marwa Ashraf Essa, Khaled M. ABDEL-HALEEM, R. El-Dahmy","doi":"10.34172/apb.2024.031","DOIUrl":"https://doi.org/10.34172/apb.2024.031","url":null,"abstract":"Purpose: The repositioning of previously approved drugs is occupying the researchers’ plans. Baclofen (Bac) was our candidate for its established neuroprotective capacity, with a proposal of efficient drug delivery as non-ionic surfactant-based nanovesicles (NISNV) formulae against mild repetitive traumatic brain injury (mRTBI) in rats, thus reducing the number of orally or injected medications, especially in severely comatose patients or pediatrics. Methods: A (23) factorial design was implemented for confining Bac-loaded NISNV formulae, where a bunch of variables were inspected. An in-vivo experiment was done to test the prepared formula’s efficacy transdermally. The following parameters were measured: brain expression of gamma amino butyric acid B (GABAB), protein kinase C- α (PKC-α), focal adhesion kinase (FAK), TNF-α and nuclear factor Kappa B (NF-κB) p65, MDA, SOD, and histopathology. Results: The PS and EE% speckled from 60.40±0.28% to 88.02±0.01% for the former and 174.64±0.93 to 1174.50±3.54 nm for the latter. In-vitro release% after 8 hours ranged from 63.25±5.47% to 84.79±3.75%. The optimized formula (F4) illustrated desirability =1, with 630.09±3.53 µg/cm2 of Bac permeated over 8 hours, which equates to 100% of Bac. Bac post-trauma treatment restored brain expression of GABAB and PKC-α, while decreasing FAK. Besides enhancing the histological findings, the anti-inflammatory effect was clear by decreasing TNF-α and NF-κB p65. Consequently, significant antioxidant sequelae were revealed herein by diminishing MDA levels and restoring SOD activity. Conclusion: Transdermal delivery of Bac-loaded niosomes confirmed neuroprotection and succeeded in surpassing skin-to-brain barriers, which makes it a promising therapeutic option for repeated traumas.","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140256146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Simultaneous Effects of miR-145-5p and hsa-let-7a-3p on Colorectal Tumorigenesis: In Vitro Evidence.","authors":"Nazila Mozammel, Elham Baghbani, Mohammad Amini, Sheyda Jodeiry Zaer, Yalda Baghay Esfandyari, Maryam Tohidast, Seyed Samad Hosseini, Seyed Ali Rahmani, Ahad Mokhtarzadeh, Behzad Baradaran","doi":"10.34172/apb.2024.004","DOIUrl":"10.34172/apb.2024.004","url":null,"abstract":"<p><strong>Purpose: </strong>MicroRNAs (miRNAs) are a group of small regulatory non-coding RNAs, which are dysregulated through tumor progression. let-7 and MIR-145 are both tumor suppressor microRNAs that are downregulated in a wide array of cancers including colorectal cancer (CRC).</p><p><strong>Methods: </strong>This study was aimed to investigate the effect of simultaneous replacement of these two tumor suppressor miRNAs on proliferation, apoptosis, and migration of CRC cells. HCT-116 with lower expression levels of hsa-let-7a-3p and MIR-145-5p was selected for functional investigations. The cells were cultured and transfected with hsa-let-7a and MIR-145, separately and in combination. Cell viability and apoptosis rates were assessed by MTT assay and flow cytometry, respectively. Cell cycle status was further evaluated using flow cytometry and qRT-PCR was employed to evaluate gene expression.</p><p><strong>Results: </strong>The obtained results showed that exogenous overexpression of MIR-145 and hsa-let-7a in HCT-116 cells could cooperatively decrease CRC cell proliferation and induce sub-G1 cell cycle arrest. Moreover, hsa-let-7a and MIR-145 co-transfection significantly increased apoptosis induction compared to separate transfected cells and control through modulating the expression levels of apoptosis-related genes including <i>Bax</i>, <i>Bcl-2</i>, <i>P53</i>, <i>Caspase-3</i>, <i>Caspase-8</i>, and <i>Caspase-9</i>. Furthermore, qRT-PCR results illustrated that hsa-let-7a and MIR-145 combination more effectively downregulated <i>MMP-9</i> and <i>MMP-2</i> expression, as the important modulators of metastasis, compared to the controls.</p><p><strong>Conclusion: </strong>Taken together, considering that exogenous overexpression of MIR-145 and hsa-let-7a showed cooperative anti-cancer effects on CRC cells, their combination may be considered as a novel therapeutic strategy for the treatment of CRC.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43108673","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":"Immunomodulating Phytochemicals: An Insight Into Their Potential Use in Cytokine Storm Situations.","authors":"Abdusalam Abdullah Alarabei, Nur Aimi Liyana Abd Aziz, Nur Izah Ab Razak, Razif Abas, Hasnah Bahari, Maizaton Atmadini Abdullah, Mohd Khairi Hussain, Amin Malik Shah Abdul Majid, Rusliza Basir","doi":"10.34172/apb.2024.001","DOIUrl":"10.34172/apb.2024.001","url":null,"abstract":"<p><p>Phytochemicals are compounds found in plants that possess a variety of bioactive properties, including antioxidant and immunomodulatory properties. Recent studies have highlighted the potential of phytochemicals in targeting specific signalling pathways involved in cytokine storm, a life-threatening clinical condition resulting from excessive immune cell activation and oversupply of proinflammatory cytokines. Several studies have documented the immunomodulatory effects of phytochemicals on immune function, including their ability to regulate essential cellular and molecular interactions of immune system cells. This makes them a promising alternative for cytokine storm management, especially when combined with existing chemotherapies. Furthermore, phytochemicals have been found to target multiple signalling pathways, including the TNF-α/NF-κB, IL-1/NF-κB, IFN-γ/JAK/STAT, and IL-6/JAK-STAT. These pathways play critical roles in the development and progression of cytokine storm, and targeting them with phytochemicals represents a promising strategy for controlling cytokine release and the subsequent inflammation. Studies have also investigated certain families of plant-related constituents and their potential immunomodulatory actions. In vivo and in vitro studies have reported the immunomodulatory effects of phytochemicals, which provide viable alternatives in the management of cytokine storm syndrome. The collective data from previous studies suggest that phytochemicals represent a potentially functional source of cytokine storm treatment and promote further exploration of these compounds as immunomodulatory agents for suppressing specific signalling cascade responses. Overall, the previous research findings support the use of phytochemicals as a complementary approach in managing cytokine storm and improving patient outcomes.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48105365","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":"Chitosan/Hyaluronan and Alginate-Nanohydroxyapatite Biphasic Scaffold as a Promising Matrix for Osteoarthritis Disorders.","authors":"Seyed Abdolvahab Banihashemian, Soheila Zamanlui Benisi, Simzar Hosseinzadeh, Shahrokh Shojaei, Hojjat Allah Abbaszadeh","doi":"10.34172/apb.2024.005","DOIUrl":"10.34172/apb.2024.005","url":null,"abstract":"<p><strong>Purpose: </strong>Regenerative medicine offers new techniques for osteoarthritis (OA) disorders, especially while considering simultaneous chondral and subchondral regenerations.</p><p><strong>Methods: </strong>Chitosan and hyaluronan were chemically bound as the chondral phase and the osteogenic layer was prepared with alginate and nano-hydroxyapatite (nHAP). These scaffolds were fixed by fibrin glue as a biphasic scaffold and then examined.</p><p><strong>Results: </strong>Scanning electron microscopy (SEM) confirmed the porosity of 61.45±4.51 and 44.145±2.81 % for the subchondral and chondral layers, respectively. The composition analysis by energy dispersive X-ray (EDAX) indicated the various elements of both hydrogels. Also, their mechanical properties indicated that the highest modulus and resistance values corresponded to the biphasic hydrogel as 108.33±5.56 and 721.135±8.21 kPa, despite the same strain value as other groups. Their individual examinations demonstrated the proteoglycan synthesis of the chondral layer and also, the alkaline phosphatase (ALP) activity of the subchondral layer as 13.3±2.2 ng. After 21 days, the cells showed a mineralized surface and a polygonal phenotype, confirming their commitment to bone and cartilage tissues, respectively. Immunostaining of collagen I and II represented greater extracellular matrix (ECM) secretion in the biphasic composite group due to the paracrine effect of the two cell types on each other.</p><p><strong>Conclusion: </strong>For the first time, the ability of this biphasic scaffold to regenerate both tissue types was evaluated and the results showed satisfactory cellular commitment to bone and cartilage tissues. Thus, this scaffold can be considered a new strategy for the preparation of implants for OA.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44569819","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":"ChatGPT in Drug Discovery Process.","authors":"Ammu V V V Ravi Kiran, Garikapati Kusuma Kumari, Praveen T Krishnamurthy","doi":"10.34172/apb.2024.007","DOIUrl":"10.34172/apb.2024.007","url":null,"abstract":"","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45149799","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":"Erythrocytes Nanoparticle Delivery: A Boon for Targeting Tumor.","authors":"Adnan Rehmatullah Siddique, Geeta Sameer Bhagwat","doi":"10.34172/apb.2023.080","DOIUrl":"10.34172/apb.2023.080","url":null,"abstract":"<p><p>Although nanoparticles (NPs) have many advantages as drug delivery systems, their poor stability in circulation, premature drug release, and nonspecific uptake in non-target organs have prompted biomimetic approaches to camouflage nano vehicles using natural cell membranes. Among them, which are extensively studied in erythrocytes, are the most abundant circulating blood cells. They are specially used for biomimetic coating on artificial NPs due to their excellent properties of good biocompatibility, biodegradability, non-immunogenicity, and long-term blood circulation. Erythrocyte-mimicking nanoparticles (EM-NPs) are prepared by combining nanoparticle cores with naturally derived erythrocyte (red blood cell or RBC) membranes. Compared with conventional nanosystems, EM-NPs hold the preferable characteristics of prolonged blood circulation time and immune evasion. In this review, the biomimetic platform of erythrocyte membrane-coated NPs is described in various aspects, with particular focus placed on the coating mechanism, preparation methods, characterization method, and recent advances in the biomedical applications of EM-NPs concerning cancer and targeted delivery.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46974888","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":"Cobalt/Bioglass Nanoparticles Enhanced Dermal Regeneration in a 3-Layered Electrospun Scaffold.","authors":"Zahra Hemmati Dezaki, Kazem Parivar, Vahabodin Goodarzi, Mohamad Reza Nourani","doi":"10.34172/apb.2024.006","DOIUrl":"10.34172/apb.2024.006","url":null,"abstract":"<p><strong>Purpose: </strong>Due to the multilayered structure of the skin tissue, the architecture of its engineered scaffolds needs to be improved. In the present study, 45s5 bioglass nanoparticles were selected to induce fibroblast proliferation and their protein secretion, although cobalt ions were added to increase their potency.</p><p><strong>Methods: </strong>A 3-layer scaffold was designed as polyurethane (PU) - polycaprolactone (PCL)/ collagen/nanoparticles-PCL/collagen. The scaffolds examined by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), tensile, surface hydrophilicity and weight loss. Biological tests were performed to assess cell survival, adhesion and the pattern of gene expression.</p><p><strong>Results: </strong>The mechanical assay showed the highest young modulus for the scaffold with the doped nanoparticles and the water contact angle of this scaffold after chemical crosslinking of collagen was reduced to 52.34±7.7°. In both assessments, the values were statistically compared to other groups. The weight loss of the corresponding scaffold was the highest value of 82.35±4.3 % due to the alkaline effect of metal ions and indicated significant relations in contrast to the scaffold with non-doped particles and bare one (<i>P</i> value<0.05). Moreover, better cell expansion, greater cell confluence and a lower degree of toxicity were confirmed. The up-regulation of TGF β1 and VEGF genes introduced this scaffold as a better model for the fibroblasts commitment to a new skin tissue among bare and nondoped scaffold (<i>P</i> value<0.05).</p><p><strong>Conclusion: </strong>The 3-layered scaffold which is loaded with cobalt ions-bonded bioglass nanoparticles, is a better substrate for the culture of the fibroblasts.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43650883","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":"The Role of the JAK-STAT Signaling Pathway in the Protective Effects of Hepatic Ischemia Post-conditioning Against the Injury Induced by Ischemia/Reperfusion in the Rat Liver.","authors":"Neda Ghasemi Pour Afshar, Hossein Ali Arab, Akram Vatannejad, Ghorbangol Ashabi, Ali Akbar Golabchifar","doi":"10.34172/apb.2024.003","DOIUrl":"10.34172/apb.2024.003","url":null,"abstract":"<p><strong>Purpose: </strong>Hepatic ischemic post-conditioning (IPOC) is shown to protect the liver from injury induced by ischemia/reperfusion (IR). However, the mechanism underlying this protection has remained elusive. The present study aimed to investigate the role of the <i>interleukin 6-Janus</i> kinase-signal transducers and activators of transcription (IL-6-JAK-STAT) pathway in the protective effect of hepatic IPOC against the IR-induced injury in the liver.</p><p><strong>Methods: </strong>Twenty-five rats were randomly divided into 5 groups of (1) sham-operated, (2) IR, (3) IR+hepatic IPOC, (4) IR+tofacitinib (TOFA), and (5) IR+TOFA+hepatic IPOC. The changes induced by IR and the effects of different treatments were assessed by enzyme release, histopathological observations, the serum level of IL-6, and the occurrence of apoptosis detected via the expression of the Bax/Bcl-2 ratio.</p><p><strong>Results: </strong>The hepatic IPOC improved the liver injury induced by IR as shown by histological changes, reduction of IL-6 level, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) compared to the IR group (<i>P</i><0.001, <i>P</i><0.05, <i>P</i><0.05, respectively). There was also downregulation of the Bax/Bcl2 ratio in the rats exposed to IR+hepatic IPOC compared with those in the IR group (<i>P</i><0.05). However, TOFA, an inhibitor of JAK-STAT activity, inhibited the protective effect of hepatic IPOC.</p><p><strong>Conclusion: </strong>It suggests that the protective effect of hepatic IPOC against IR-induced injury may be mediated by activating the IL-6-JAK-STAT pathway.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46684894","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}