984,992 results on '"Apoptosis"'
Search Results
2. Inhibiting liver autophagy and promoting hepatocyte apoptosis by 'Schistosoma japonicum' infection
- Author
-
Yu, Zhihao, Jiang, Tingting, Xu, Fangfang, Jing, Zhang, Hu, Yuan, and Cao, Jianping
- Published
- 2024
3. A therapy for suppressing canonical and noncanonical SARS-CoV-2 viral entry and an intrinsic intrapulmonary inflammatory response
- Author
-
Leibel, Sandra L, McVicar, Rachael N, Murad, Rabi, Kwong, Elizabeth M, Clark, Alex E, Alvarado, Asuka, Grimmig, Bethany A, Nuryyev, Ruslan, Young, Randee E, Lee, Jamie C, Peng, Weiqi, Zhu, Yanfang P, Griffis, Eric, Nowell, Cameron J, James, Brian, Alarcon, Suzie, Malhotra, Atul, Gearing, Linden J, Hertzog, Paul J, Galapate, Cheska M, Galenkamp, Koen MO, Commisso, Cosimo, Smith, Davey M, Sun, Xin, Carlin, Aaron F, Sidman, Richard L, Croker, Ben A, and Snyder, Evan Y
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Biological Sciences ,Stem Cell Research - Induced Pluripotent Stem Cell ,Stem Cell Research ,Infectious Diseases ,Stem Cell Research - Induced Pluripotent Stem Cell - Human ,Lung ,Coronaviruses ,Emerging Infectious Diseases ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Infection ,Humans ,SARS-CoV-2 ,COVID-19 ,Virus Internalization ,Organoids ,COVID-19 Drug Treatment ,Induced Pluripotent Stem Cells ,Angiotensin-Converting Enzyme 2 ,Inflammation ,Cytokines ,Apoptosis ,inflammation ,lung organoids ,macropinocytosis ,surfactant - Abstract
The prevalence of "long COVID" is just one of the conundrums highlighting how little we know about the lung's response to viral infection, particularly to syndromecoronavirus-2 (SARS-CoV-2), for which the lung is the point of entry. We used an in vitro human lung system to enable a prospective, unbiased, sequential single-cell level analysis of pulmonary cell responses to infection by multiple SARS-CoV-2 strains. Starting with human induced pluripotent stem cells and emulating lung organogenesis, we generated and infected three-dimensional, multi-cell-type-containing lung organoids (LOs) and gained several unexpected insights. First, SARS-CoV-2 tropism is much broader than previously believed: Many lung cell types are infectable, if not through a canonical receptor-mediated route (e.g., via Angiotensin-converting encyme 2(ACE2)) then via a noncanonical "backdoor" route (via macropinocytosis, a form of endocytosis). Food and Drug Administration (FDA)-approved endocytosis blockers can abrogate such entry, suggesting adjunctive therapies. Regardless of the route of entry, the virus triggers a lung-autonomous, pulmonary epithelial cell-intrinsic, innate immune response involving interferons and cytokine/chemokine production in the absence of hematopoietic derivatives. The virus can spread rapidly throughout human LOs resulting in mitochondrial apoptosis mediated by the prosurvival protein Bcl-xL. This host cytopathic response to the virus may help explain persistent inflammatory signatures in a dysfunctional pulmonary environment of long COVID. The host response to the virus is, in significant part, dependent on pulmonary Surfactant Protein-B, which plays an unanticipated role in signal transduction, viral resistance, dampening of systemic inflammatory cytokine production, and minimizing apoptosis. Exogenous surfactant, in fact, can be broadly therapeutic.
- Published
- 2024
4. Differential susceptibility of cells infected with defective and intact HIV proviruses to killing by obatoclax and other small molecules
- Author
-
Kadiyala, Gayatri Nikhila, Telwatte, Sushama, Wedrychowski, Adam, Janssens, Julie, Kim, Sun Jin, Kim, Peggy, Deeks, Steven, Wong, Joseph K, and Yukl, Steven A
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,HIV/AIDS ,Infectious Diseases ,Sexually Transmitted Infections ,Genetics ,5.1 Pharmaceuticals ,6.1 Pharmaceuticals ,Infection ,Humans ,Indoles ,HIV Infections ,Pyrroles ,Leukocytes ,Mononuclear ,Proviruses ,apoptosis ,Bcl-2 ,DNA ,HIV ,IAP ,interferon ,mTOR ,PD-1 ,proteasome ,RIG-I ,TLR7 ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectivesSome drugs that augment cell-intrinsic defenses or modulate cell death/survival pathways have been reported to selectively kill cells infected with HIV or Simian Immunodeficiency Virus (SIV), but comparative studies are lacking. We hypothesized that these drugs may differ in their ability to kill cells infected with intact and defective proviruses.DesignTo investigate this hypothesis, drugs were tested ex vivo on peripheral blood mononuclear cells (PBMC) from nine antiretroviral therapy (ART)-suppressed individuals.MethodsWe tested drugs currently in clinical use or human trials, including auranofin (p53 modulator), interferon alpha2A, interferon gamma, acitretin (RIG-I inducer), GS-9620/vesatolimod (TLR7 agonist), nivolumab (PD-1 blocker), obatoclax (Bcl-2 inhibitor), birinapant [inhibitor of apoptosis proteins (IAP) inhibitor], bortezomib (proteasome inhibitor), and INK128/sapanisertib [mammalian target of rapamycin mTOR] [c]1/2 inhibitor). After 6 days of treatment, we measured cell counts/viabilities and quantified levels of total, intact, and defective HIV DNA by droplet digital PCR (Intact Proviral DNA Assay).ResultsObatoclax reduced intact HIV DNA [median = 27-30% of dimethyl sulfoxide control (DMSO)] but not defective or total HIV DNA. Other drugs showed no statistically significant effects.ConclusionObatoclax and other Bcl-2 inhibitors deserve further study in combination therapies aimed at reducing the intact HIV reservoir in order to achieve a functional cure and/or reduce HIV-associated immune activation.
- Published
- 2024
5. IRX4204 Induces Senescence and Cell Death in HER2-positive Breast Cancer and Synergizes with Anti-HER2 Therapy.
- Author
-
Moyer, Cassandra, Lanier, Amanda, Qian, Jing, Coleman, Darian, Hill, Jamal, Vuligonda, Vidyasagar, Sanders, Martin, Mazumdar, Abhijit, and Brown, Powel
- Subjects
Humans ,Animals ,Breast Neoplasms ,Female ,Receptor ,ErbB-2 ,Mice ,Cell Line ,Tumor ,Xenograft Model Antitumor Assays ,Drug Synergism ,Cellular Senescence ,Cell Proliferation ,Apoptosis ,Trastuzumab ,Drug Resistance ,Neoplasm ,Retinoids - Abstract
PURPOSE: Rexinoids, agonists of nuclear retinoid X receptor (RXR), have been used for the treatment of cancers and are well tolerated in both animals and humans. However, the usefulness of rexinoids in treatment of breast cancer remains unknown. This study examines the efficacy of IRX4204, a highly specific rexinoid, in breast cancer cell lines and preclinical models to identify a biomarker for response and potential mechanism of action. EXPERIMENTAL DESIGN: IRX4204 effects on breast cancer cell growth and viability were determined using cell lines, syngeneic mouse models, and primary patient-derived xenograft (PDX) tumors. In vitro assays of cell cycle, apoptosis, senescence, and lipid metabolism were used to uncover a potential mechanism of action. Standard anti-HER2 therapies were screened in combination with IRX4204 on a panel of breast cancer cell lines to determine drug synergy. RESULTS: IRX4204 significantly inhibits the growth of HER2-positive breast cancer cell lines, including trastuzumab and lapatinib-resistant JIMT-1 and HCC1954. Treatment with IRX4204 reduced tumor growth rate in the MMTV-ErbB2 mouse and HER2-positive PDX model by 49% and 44%, respectively. Mechanistic studies revealed IRX4204 modulates lipid metabolism and induces senescence of HER2-positive cells. In addition, IRX4204 demonstrates additivity and synergy with HER2-targeted mAbs, tyrosine kinase inhibitors, and antibody-drug conjugates. CONCLUSIONS: These findings identify HER2 as a biomarker for IRX4204 treatment response and demonstrate a novel use of RXR agonists to synergize with current anti-HER2 therapies. Furthermore, our results suggest that RXR agonists can be useful for the treatment of anti-HER2 resistant and metastatic HER2-positive breast cancer.
- Published
- 2024
6. Critical roles of tubular mitochondrial ATP synthase dysfunction in maleic acid-induced acute kidney injury.
- Author
-
Lin, Hugo, Liang, Chan-Jung, Yang, Ming-Yu, Chen, Phang-Lang, Wang, Tzu-Ming, Chen, Yen-Hua, Shih, Yao-Hsiang, Liu, Wangta, Chiu, Chien-Chih, Chiang, Chih-Kang, Lin, Chang-Shen, and Lin, Han-Chen
- Subjects
AKI ,ATP synthase ,Maleic acid ,Mitochondria ,Animals ,Humans ,Male ,Mice ,Acute Kidney Injury ,Apoptosis ,Cell Line ,Epithelial Cells ,Kidney Tubules ,Proximal ,Maleates ,Mice ,Inbred C57BL ,Mitochondria ,Mitochondrial Proton-Translocating ATPases ,Reactive Oxygen Species - Abstract
Maleic acid (MA) induces renal tubular cell dysfunction directed to acute kidney injury (AKI). AKI is an increasing global health burden due to its association with mortality and morbidity. However, targeted therapy for AKI is lacking. Previously, we determined mitochondrial-associated proteins are MA-induced AKI affinity proteins. We hypothesized that mitochondrial dysfunction in tubular epithelial cells plays a critical role in AKI. In vivo and in vitro systems have been used to test this hypothesis. For the in vivo model, C57BL/6 mice were intraperitoneally injected with 400 mg/kg body weight MA. For the in vitro model, HK-2 human proximal tubular epithelial cells were treated with 2 mM or 5 mM MA for 24 h. AKI can be induced by administration of MA. In the mice injected with MA, the levels of blood urea nitrogen (BUN) and creatinine in the sera were significantly increased (p
- Published
- 2024
7. Tumor mitochondrial oxidative phosphorylation stimulated by the nuclear receptor RORγ represents an effective therapeutic opportunity in osteosarcoma.
- Author
-
Zheng, Jianwei, Wang, Qianqian, Chen, Jianghe, Cai, Guodi, Zhang, Zhenhua, Zou, Hongye, Zou, June, Liu, Qianqian, Ji, Shufeng, Shao, Guoli, Li, Hong, Li, Sheng, Chen, Hongwu, Lu, LinLin, Yuan, Yanqiu, Liu, Peiqing, and Wang, Junjian
- Subjects
Osteosarcoma ,Humans ,Oxidative Phosphorylation ,Mitochondria ,Nuclear Receptor Subfamily 1 ,Group F ,Member 3 ,Cell Line ,Tumor ,Animals ,Bone Neoplasms ,Mice ,Reactive Oxygen Species ,Apoptosis ,Gene Expression Regulation ,Neoplastic ,Ferroptosis ,Mice ,Nude ,Male ,Cell Proliferation ,RNA-Binding Proteins - Abstract
Osteosarcoma (OS) is the most common malignant bone tumor with a poor prognosis. Here, we show that the nuclear receptor RORγ may serve as a potential therapeutic target in OS. OS exhibits a hyperactivated oxidative phosphorylation (OXPHOS) program, which fuels the carbon source to promote tumor progression. We found that RORγ is overexpressed in OS tumors and is linked to hyperactivated OXPHOS. RORγ induces the expression of PGC-1β and physically interacts with it to activate the OXPHOS program by upregulating the expression of respiratory chain component genes. Inhibition of RORγ strongly inhibits OXPHOS activation, downregulates mitochondrial functions, and increases ROS production, which results in OS cell apoptosis and ferroptosis. RORγ inverse agonists strongly suppressed OS tumor growth and progression and sensitized OS tumors to chemotherapy. Taken together, our results indicate that RORγ is a critical regulator of the OXPHOS program in OS and provides an effective therapeutic strategy for this deadly disease.
- Published
- 2024
8. Pretreatment with IL-15 and IL-18 rescues natural killer cells from granzyme B-mediated apoptosis after cryopreservation.
- Author
-
Berjis, Abdulla, Muthumani, Deeksha, Aguilar, Oscar, Pomp, Oz, Johnson, Omar, Finck, Amanda, Engel, Nils, Chen, Linhui, Plachta, Nicolas, Scholler, John, Lanier, Lewis, June, Carl, and Sheppard, Neil
- Subjects
Granzymes ,Interleukin-15 ,Killer Cells ,Natural ,Apoptosis ,Humans ,Interleukin-18 ,Animals ,Cryopreservation ,Mice ,Cell Line ,Tumor ,CRISPR-Cas Systems - Abstract
Human natural killer (NK) cell-based therapies are under assessment for treating various cancers, but cryopreservation reduces both the recovery and function of NK cells, thereby limiting their therapeutic feasibility. Using cryopreservation protocols optimized for T cells, here we find that ~75% of NK cells die within 24 h post-thaw, with the remaining cells displaying reduced cytotoxicity. Using CRISPR-Cas9 gene editing and confocal microscopy, we find that cryopreserved NK cells largely die via apoptosis initiated by leakage of granzyme B from cytotoxic vesicles. Pretreatment of NK cells with a combination of Interleukins-15 (IL-15) and IL-18 prior to cryopreservation improves NK cell recovery to ~90-100% and enables equal tumour control in a xenograft model of disseminated Raji cell lymphoma compared to non-cryopreserved NK cells. The mechanism of IL-15 and IL-18-induced protection incorporates two mechanisms: a transient reduction in intracellular granzyme B levels via degranulation, and the induction of antiapoptotic genes.
- Published
- 2024
9. Targeting host deoxycytidine kinase mitigates Staphylococcus aureus abscess formation.
- Author
-
Winstel, Volker, Abt, Evan, Le, Thuc, and Radu, Caius
- Subjects
Staphylococcus aureus ,apoptosis ,infectious disease ,macrophages ,microbiology ,Animals ,Humans ,Staphylococcus aureus ,Deoxycytidine Kinase ,Abscess ,Staphylococcal Infections ,Anti-Infective Agents ,Mammals - Abstract
Host-directed therapy (HDT) is an emerging approach to overcome antimicrobial resistance in pathogenic microorganisms. Specifically, HDT targets host-encoded factors required for pathogen replication and survival without interfering with microbial growth or metabolism, thereby eliminating the risk of resistance development. By applying HDT and a drug repurposing approach, we demonstrate that (R)-DI-87, a clinical-stage anticancer drug and potent inhibitor of mammalian deoxycytidine kinase (dCK), mitigates Staphylococcus aureus abscess formation in organ tissues upon invasive bloodstream infection. Mechanistically, (R)-DI-87 shields phagocytes from staphylococcal death-effector deoxyribonucleosides that target dCK and the mammalian purine salvage pathway-apoptosis axis. In this manner, (R)-DI-87-mediated protection of immune cells amplifies macrophage infiltration into deep-seated abscesses, a phenomenon coupled with enhanced pathogen control, ameliorated immunopathology, and reduced disease severity. Thus, pharmaceutical blockade of dCK represents an advanced anti-infective intervention strategy against which staphylococci cannot develop resistance and may help to fight fatal infectious diseases in hospitalized patients.
- Published
- 2024
10. The novel drug candidate S2/IAPinh improves survival in models of pancreatic and ovarian cancer.
- Author
-
Hagi, Takaomi, Vangveravong, Suwanna, Takchi, Rony, Gong, Qingqing, Goedegebuure, S, Tiriac, Herve, Van Tine, Brian, Powell, Matthew, Hawkins, William, and Spitzer, Dirk
- Subjects
Humans ,Animals ,Mice ,Female ,Antineoplastic Agents ,Apoptosis ,Ovarian Neoplasms ,Inhibitor of Apoptosis Proteins ,Caspases ,Cell Line ,Tumor - Abstract
Cancer selective apoptosis remains a therapeutic challenge and off-target toxicity has limited enthusiasm for this target clinically. Sigma-2 ligands (S2) have been shown to enhance the cancer selectivity of small molecule drug candidates by improving internalization. Here, we report the synthesis of a novel drug conjugate, which was created by linking a clinically underperforming SMAC mimetic (second mitochondria-derived activator of caspases; LCL161), an inhibitor (antagonist) of inhibitor of apoptosis proteins (IAPinh) with the sigma-2 ligand SW43, resulting in the new chemical entity S2/IAPinh. Drug potency was assessed via cell viability assays across several pancreatic and ovarian cancer cell lines in comparison with the individual components (S2 and IAPinh) as well as their equimolar mixtures (S2 + IAPinh) both in vitro and in preclinical models of pancreatic and ovarian cancer. Mechanistic studies of S2/IAPinh-mediated cell death were investigated in vitro and in vivo using syngeneic and xenograft mouse models of murine pancreatic and human ovarian cancer, respectively. S2/IAPinh demonstrated markedly improved pharmacological activity in cancer cell lines and primary organoid cultures when compared to the controls. In vivo testing demonstrated a marked reduction in tumor growth rates and increased survival rates when compared to the respective control groups. The predicted mechanism of action of S2/IAPinh was confirmed through assessment of apoptosis pathways and demonstrated strong target degradation (cellular inhibitor of apoptosis proteins-1 [cIAP-1]) and activation of caspases 3 and 8. Taken together, S2/IAPinh demonstrated efficacy in models of pancreatic and ovarian cancer, two challenging malignancies in need of novel treatment concepts. Our data support an in-depth investigation into utilizing S2/IAPinh for the treatment of cancer.
- Published
- 2024
11. The clustered gamma protocadherin PcdhγC4 isoform regulates cortical interneuron programmed cell death in the mouse cortex.
- Author
-
Leon, Walter, Steffen, David, Dale-Huang, Fiona, Rakela, Benjamin, Breevoort, Arnar, Romero-Rodriguez, Ricardo, Hasenstaub, Andrea, Weiner, Joshua, Alvarez-Buylla, Arturo, and Stryker, Michael
- Subjects
GABAergic ,inhibitory neurons ,medial ganglionic eminence ,neuronal elimination ,transplantation ,Mice ,Animals ,Humans ,Protocadherins ,Interneurons ,Neurons ,Apoptosis ,Protein Isoforms ,Cerebral Cortex - Abstract
Cortical inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into the cortex where they make connections with locally produced excitatory glutamatergic neurons. Cortical function critically depends on the number of cINs, which is also key to establishing the appropriate inhibitory/excitatory balance. The final number of cINs is determined during a postnatal period of programmed cell death (PCD) when ~40% of the young cINs are eliminated. Previous work shows that the loss of clustered gamma protocadherins (Pcdhgs), but not of genes in the Pcdha or Pcdhb clusters, dramatically increased BAX-dependent cIN PCD. Here, we show that PcdhγC4 is highly expressed in cINs of the mouse cortex and that this expression increases during PCD. The sole deletion of the PcdhγC4 isoform, but not of the other 21 isoforms in the Pcdhg gene cluster, increased cIN PCD. Viral expression of the PcdhγC4, in cIN lacking the function of the entire Pcdhg cluster, rescued most of these cells from cell death. We conclude that PcdhγC4 plays a critical role in regulating the survival of cINs during their normal period of PCD. This highlights how a single isoform of the Pcdhg cluster, which has been linked to human neurodevelopmental disorders, is essential to adjust cIN cell numbers during cortical development.
- Published
- 2024
12. Stress response silencing by an E3 ligase mutated in neurodegeneration.
- Author
-
Haakonsen, Diane, Heider, Michael, Ingersoll, Andrew, Vodehnal, Kayla, Witus, Samuel, Uenaka, Takeshi, Wernig, Marius, and Rapé, Michael
- Subjects
Apoptosis ,Ataxia ,Cell Survival ,Dementia ,Mitochondria ,Mitochondrial Proteins ,Multiprotein Complexes ,Mutation ,Neurodegenerative Diseases ,Protein Stability ,Protein Transport ,Proteolysis ,Stress ,Physiological ,Ubiquitin ,Ubiquitin-Protein Ligases ,Ubiquitination - Abstract
Stress response pathways detect and alleviate adverse conditions to safeguard cell and tissue homeostasis, yet their prolonged activation induces apoptosis and disrupts organismal health1-3. How stress responses are turned off at the right time and place remains poorly understood. Here we report a ubiquitin-dependent mechanism that silences the cellular response to mitochondrial protein import stress. Crucial to this process is the silencing factor of the integrated stress response (SIFI), a large E3 ligase complex mutated in ataxia and in early-onset dementia that degrades both unimported mitochondrial precursors and stress response components. By recognizing bifunctional substrate motifs that equally encode protein localization and stability, the SIFI complex turns off a general stress response after a specific stress event has been resolved. Pharmacological stress response silencing sustains cell survival even if stress resolution failed, which underscores the importance of signal termination and provides a roadmap for treating neurodegenerative diseases caused by mitochondrial import defects.
- Published
- 2024
13. Engrailed‐1 Promotes Pancreatic Cancer Metastasis
- Author
-
Xu, Jihao, Roe, Jae‐Seok, Lee, EunJung, Tonelli, Claudia, Ji, Keely Y, Younis, Omar W, Somervile, Tim DD, Yao, Melissa, Milazzo, Joseph P, Tiriac, Herve, Kolarzyk, Anna M, Lee, Esak, Grem, Jean L, Lazenby, Audrey J, Grunkemeyer, James A, Hollingsworth, Michael A, Grandgenett, Paul M, Borowsky, Alexander D, Park, Youngkyu, Vakoc, Christopher R, Tuveson, David A, and Hwang, Chang‐Il
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Pancreatic Cancer ,Genetics ,Rare Diseases ,Biotechnology ,Digestive Diseases ,Humans ,Transcription Factors ,Pancreatic Neoplasms ,Gene Expression Regulation ,Carcinoma ,Pancreatic Ductal ,apoptosis ,cancer progression ,cancer therapeutics ,developmental transcription factor ,Engrailed-1 ,epigenetic reprogramming ,ERK signaling ,metastasis ,pancreatic ductal adenocarcinoma - Abstract
Engrailed-1 (EN1) is a critical homeodomain transcription factor (TF) required for neuronal survival, and EN1 expression has been shown to promote aggressive forms of triple negative breast cancer. Here, it is reported that EN1 is aberrantly expressed in a subset of pancreatic ductal adenocarcinoma (PDA) patients with poor outcomes. EN1 predominantly repressed its target genes through direct binding to gene enhancers and promoters, implicating roles in the activation of MAPK pathways and the acquisition of mesenchymal cell properties. Gain- and loss-of-function experiments demonstrated that EN1 promoted PDA transformation and metastasis in vitro and in vivo. The findings nominate the targeting of EN1 and downstream pathways in aggressive PDA.
- Published
- 2024
14. Neuroprotective Activity of Strawberry Tree (Arbutus unedo L.) Against Formaldehyde-Induced Oxidative Stress in The Rat Hippocampus/Actividad Neuroprotectora del Madrono (Arbutus Unedo L.) contra el Estres Oxidativo Inducido por Formaldehido en el Hipocampo de Rata
- Author
-
Erdogan, Mehtap, Colak, Tuncay, Ceylan, Fatma Sureyya, Kir, Hale Maral, Kurnaz, Sema, Ozsoy, Ozgur Doga, and Sahin, Zuhal
- Published
- 2024
15. Green synthesis, characterization, and antiparasitic effects of gold nanoparticles against 'Echinococcus granulosus' protoscoleces
- Author
-
Raziani, Yosra, Shakib, Pegah, Rashidipour, Marzieh, Cheraghipour, Koroush, Yadegari, Javad Ghasemian, and Mahmoudvand, Hossein
- Published
- 2023
16. Manuka Honey Inhibits Human Breast Cancer Progression in Preclinical Models
- Author
-
Márquez-Garbán, Diana C, Yanes, Cristian D, Llarena, Gabriela, Elashoff, David, Hamilton, Nalo, Hardy, Mary, Wadehra, Madhuri, McCloskey, Susan A, and Pietras, Richard J
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Women's Health ,Breast Cancer ,Cancer ,5.1 Pharmaceuticals ,Humans ,Honey ,Breast Neoplasms ,Female ,Animals ,Apoptosis ,MCF-7 Cells ,Cell Proliferation ,Signal Transduction ,Mice ,Xenograft Model Antitumor Assays ,Mice ,Nude ,Leptospermum ,TOR Serine-Threonine Kinases ,Proto-Oncogene Proteins c-akt ,Antineoplastic Agents ,STAT3 Transcription Factor ,Disease Progression ,AMP-Activated Protein Kinases ,Cell Line ,Tumor ,Phosphorylation ,Manuka honey ,breast cancer ,estrogen receptor-positive breast cancer ,triple-negative breast cancer ,in vivo xenografts ,AMP kinase signaling ,mTOR ,STAT3 ,Food Sciences ,Nutrition and Dietetics ,Clinical sciences ,Nutrition and dietetics ,Public health - Abstract
Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3 to 5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast cancer MCF-7 cells, but anti-proliferative effects of MH were less pronounced in MDA-MB-231 breast cancer cells. Effects of MH were also tested on non-malignant human mammary epithelial cells (HMECs) at 2.5% w/v, and it was found that MH reduced the proliferation of MCF-7 cells but not that of HMECs. Notably, the antitumor activity of MH was in the range of that exerted by treatment of MCF-7 cells with the antiestrogen tamoxifen. Further, MH treatment stimulated apoptosis of MCF-7 cells in vitro, with most cells exhibiting acute and significant levels of apoptosis that correlated with PARP activation. Additionally, the effects of MH induced the activation of AMPK and inhibition of AKT/mTOR downstream signaling. Treatment of MCF7 cells with increased concentrations of MH induced AMPK phosphorylation in a dose-dependent manner that was accompanied by inhibition of phosphorylation of AKT and mTOR downstream effector protein S6. In addition, MH reduced phosphorylated STAT3 levels in vitro, which may correlate with MH and AMPK-mediated anti-inflammatory properties. Further, in vivo, MH administered alone significantly inhibited the growth of established MCF-7 tumors in nude mice by 84%, resulting in an observable reduction in tumor volume. Our findings highlight the need for further research into the use of natural compounds, such as MH, for antitumor efficacy and potential chemoprevention and investigation of molecular pathways underlying these actions.
- Published
- 2024
17. The therapeutically actionable long non-coding RNA ‘T-RECS’ is essential to cancer cells’ survival in NRAS/MAPK-driven melanoma
- Author
-
Feichtenschlager, Valentin, Chen, Linan, Zheng, Yixuan James, Ho, Wilson, Sanlorenzo, Martina, Vujic, Igor, Fewings, Eleanor, Lee, Albert, Chen, Christopher, Callanan, Ciara, Lin, Kevin, Qu, Tiange, Hohlova, Dasha, Vujic, Marin, Hwang, Yeonjoo, Lai, Kevin, Chen, Stephanie, Nguyen, Thuan, Muñoz, Denise P, Kohwi, Yoshinori, Posch, Christian, Daud, Adil, Rappersberger, Klemens, Kohwi-Shigematsu, Terumi, Coppé, Jean-Philippe, and Ortiz-Urda, Susana
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Genetics ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Humans ,Mice ,Animals ,Melanoma ,RNA ,Long Noncoding ,Apoptosis ,Oligonucleotides ,Antisense ,Cell Line ,Tumor ,Membrane Proteins ,GTP Phosphohydrolases ,T-RECS ,lncRNA ,MAPK-pathway ,hnRNPA2/B1 ,Antisense oligonucleotides ,HT-KAM ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using a discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified a nuclear-enriched lncRNA (AC004540.4) that is upregulated in NRAS/MAPK-dependent melanoma, and that we named T-RECS. Considering potential innovative treatment strategies, we designed antisense oligonucleotides (ASOs) to target T-RECS. T-RECS ASOs reduced the growth of melanoma cells and induced apoptotic cell death, while having minimal impact on normal primary melanocytes. Mechanistically, treatment with T-RECS ASOs downregulated the activity of pro-survival kinases and reduced the protein stability of hnRNPA2/B1, a pro-oncogenic regulator of MAPK signaling. Using patient- and cell line- derived tumor xenograft mouse models, we demonstrated that systemic treatment with T-RECS ASOs significantly suppressed the growth of melanoma tumors, with no noticeable toxicity. ASO-mediated T-RECS inhibition represents a promising RNA-targeting approach to improve the outcome of MAPK pathway-activated melanoma.
- Published
- 2024
18. Extracorporeal Shockwave Therapy Alleviates Inflammatory Pain by Down-Regulating NLRP3 Inflammasome in Experimental Chronic Prostatitis and Chronic Pelvic Pain Syndrome.
- Author
-
Bae, Woong, Shin, Dongho, Piao, Jun, Kim, Soomin, Choi, Yong, Park, Bong, Jung, Hyun, Sorkhi, Samuel, Chawla, Saager, Cheon, Chung, Kang, Dae, Choi, Jong, Park, Sang-Hyuck, Kim, Sae, and Rajasekaran, Mahadevan
- Subjects
Apoptosis ,Extracorporeal shockwave therapy ,Inflammasomes ,Prostatitis - Abstract
PURPOSE: To evaluate the anti-inflammatory and antioxidative effects of extracorporeal shockwave therapy (ESWT) on prostatitis and explore the mechanism of alleviating pain. MATERIALS AND METHODS: For in vitro testing, RWPE-1 cells were randomly divided into 5 groups: (1) RWPE-1 group (normal control), (2) LPS group (lipopolysaccharide inducing inflammation), (3) 0.1ESWT group (treated by 0.1 mJ/mm² energy level), (4) 0.2ESWT group (treated by 0.2 mJ/mm² energy level), and (5) 0.3ESWT group (treated by 0.3 mJ/mm² energy level). After ESWT was administered, cells and supernatant were collected for ELISA and western blot. For in vivo testing, Sprague-Dawley male rats were randomly divided into 3 groups: (1) normal group, (2) prostatitis group, and (3) ESWT group (n=12 for each). Prostatitis was induced by 17 beta-estradiol and dihydrotestosterone (DHT) administration. Four weeks after ESWT, the pain index was assessed for all groups and prostate tissues were collected for immunohistochemistry, immunofluorescence, apoptosis analysis and, western blot. RESULTS: Our in vitro studies showed that the optimal energy flux density of ESWT was 0.2 mJ/mm². In vivo, ESWT ameliorated discomfort in rats with prostatitis and inflammation symptoms were improved. Compared to normal rats, overexpressed NLRP3 inflammasomes triggered apoptosis in rats with prostatitis and this was improved by ESWT. TLR4-NFκB pathway was overactive after experimental prostatitis, compared to normal and ESWT groups, and prostatitis induced alterations in BAX/BAK pathway were inhibited by ESWT. CONCLUSIONS: ESWT improved CP/CPPS by reducing NLRP3 inflammasome and ameliorated apoptosis via inhibiting BAX/BAK pathway in a rat model. TLR4 may play a key role in bonding NLRP3 inflammasome and BAX/BAK pathways. ESWT might be a promising approach for the treatment of CP/CPPS.
- Published
- 2024
19. Impact of Agaricus blazei Murill Extract Combined With Imatinib Treatment on the Proliferation and Apoptosis of Multidrug‐Resistant Leukemia Cells.
- Author
-
Wang, Dongping, Ge, Wanwen, Sun, Yanqing, and Santos, Mario Ferreira Conceição
- Abstract
Multidrug resistance (MDR) is a major cause of chronic myeloid leukemia (CML) relapse, therapeutic failure, and a poor prognosis. However, Agaricus blazei Murill (AbM) is a mushroom that might have anticancer and other medicinal properties. Therefore, this study aimed to determine the effects of combining the acidic RNA protein complex FA‐2‐b‐β extracted from AbM with imatinib (IM) on MDR in the K562/ADR leukemia cell line in vitro and in xenograft mouse models. The combination of FA‐2‐b‐β and IM significantly inhibited cell proliferation and promoted apoptosis in K562/ADR cells compared with either alone. Western blotting (WB) revealed that the combination significantly reduced p‐PI3K, p‐AKT, and p‐mTOR protein expression. The combination also inhibited tumor growth in mice with K562/ADR xenografts. These findings suggested that FA‐2‐b‐β enhances the effects of IM on K562/ADR cell proliferation and apoptosis, potentially by inhibiting the PI3K/AKT/mTOR pathway and downregulating P‐glycoprotein (P‐gp) expression. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
20. cba‐miR‐222‐3p involved in photoperiod‐induced apoptosis in testes of striped hamsters by targeting TRAF7.
- Author
-
WANG, Shuo, XU, Jinhui, WANG, Xingchen, WANG, Mingdi, XUE, Huiliang, WU, Ming, FAN, Chao, CHEN, Lei, and XU, Laixiang
- Abstract
The role of miRNAs in the regulation of seasonal reproduction in rodents, particularly in relation to photoperiod changes, is still poorly understood. Previous studies on miRNA transcriptomes of striped hamster (
Cricetulus barabensis ) testes have indicated that the photoperiodism of testes, especially apoptosis, may be influenced by miRNAs. As a functional miRNA, cba‐miR‐222‐3p in striped hamster testes exhibits suppression under a short photoperiod. To elucidate the potential role of testicular cba‐miR‐222‐3p in the seasonal reproduction of striped hamsters, we exposed male striped hamsters to different photoperiods or injected miRNA agomir into the testes and observed the effects of these treatments, particularly some indicators related to apoptosis. The results showed that the levels of apoptosis in the testes increased in short daylength, accompanied by a significant decrease in cba‐miR‐222‐3p expression and an increase in TRAF7 expression. Dual luciferase reporter assays verified the targeting relationship between cba‐miR‐222‐3p and TRAF7 predicted by bioinformatics. In addition, the expression of TRAF7 decreased in the testes, which injected miRNA agomir, leading to inhibition of apoptosis, and the expression of key genes (MEKK3 ,p38 ,p53 ) in the downstream MAPK signaling pathway of TRAF7 was suppressed. These results suggest that short daylength induces testicular apoptosis in striped hamsters, and one possible mechanism is that the decreased expression of miR‐222‐3p in testes reduces the repression of TRAF7 translation, thereby activating the MAPK pathway and affecting the level of testicular apoptosis. These findings reveal the potential role of miR‐222‐3p in animal reproduction and provide new insights into the regulation of rodent populations. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
21. Morin Improves the Bone Histomorphology and Biochemical Markers in an Animal Model of Ovariectomy‐Induced Osteoporosis by Suppressing Autophagy and Apoptosis.
- Author
-
Jiang, Nan, Qi, Bo, Li, Gang, Yao, Ling, and Fan, Xinyu
- Abstract
ABSTRACT Osteoporosis (OP) is the most prevalent metabolic bone disease and an important postmenopausal consequence. This study aimed to investigate the effects of morin, a flavonoid with beneficial properties, on ovariectomy‐induced OP. Animals were ovariectomized (OVX) and treated with different doses of morin (15, 30, and 45 mg/kg/day) or estradiol (10 μg/kg/day) for 10 weeks by gavage. Then bone histo‐stereology, bone‐related biochemical indicators, and gene and protein levels of autophagy and apoptosis‐related markers were analyzed. In comparison to controls, OVX significantly decreased the number of osteoblasts (5.78 × 106 vs. 1.66 × 106) and osteocytes (32.55 × 106 vs. 11.92 × 106), whereas increasing the number of osteoclasts (83.38 × 103 vs. 392.1 × 103). Moreover, OVX caused a remarkable decrease in bone structures and Ca, P, and estradiol levels while increasing ALP and OC (p < 0.001). The administration of 45 mg/kg/day morin restored the effects of OP on bone histomorphology and biochemical markers (p < 0.05). Further studies revealed that morin caused a 7.1% and 36.6% decrease in the bone level of LC3 and BECN1 proteins, respectively, compared to the OVX group. Also, morin caused a significant decrease of 47.4% in the CASP3 level and a significant increase of 23.6% in the BCL‐2 level compared to OVX animals (p < 0.001). The present findings showed that morin is potentially able to improve the bone‐related histomorphological and biochemical changes caused by osteoporosis, which is probably attributed to the suppression of apoptosis‐ and autophagy‐caused cell death. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
22. The molecular anti-metastatic potential of CBD and THC from Lebanese Cannabis via apoptosis induction and alterations in autophagy.
- Author
-
Younes, Maria, Hage, Marissa El, Shebaby, Wassim, Al Toufaily, Sahar, Ismail, Jana, Naim, Hassan Y., Mroueh, Mohammad, and Rizk, Sandra
- Abstract
The medicinal plant Cannabis sativa L. (C. sativa) is currently being extensively studied to determine the full extent of its therapeutic pharmacological potential. Δ9-tetrahydocannabinol (THC) and cannabidiol (CBD) are the most thoroughly investigated compounds. We aimed to explore the anticancer activity of cannabinoids mixture isolated from the Lebanese C. sativa plant in ratios comparable to the local medicinal plant, to elucidate its mechanism of action in breast cancer cells in vitro. Cells were subjected to cytotoxicity assay, cell cycle analysis, Annexin V/PI dual staining, cell death ELISA, immunofluorescence, in addition to western blot analysis of apoptotic and autophagy markers. We further evaluated the anti-metastatic effect of cannabinoids on MDA-MB-231 using the scratch wound-healing, trans-well migration and invasion assays. Our results revealed the promising therapeutic benefits of CBD/THC on inhibiting the growth of breast cancer cells by promoting cellular fragmentation, phosphatidylserine translocation to the outer membrane leaflet and DNA fragmentation in both cell lines while inhibiting the motility of the triple negative breast cancer cells. In our study, CBD/THC mixture was found to exhibit a pro-apoptotic activity via the activation of the mitochondrial apoptotic pathway, independent from ROS production while also suggesting the activation of a caspase-dependent apoptotic pathway. Even though autophagy was altered upon exposure to the cannabinoid mixture, our data suggested that it is not the mechanism responsible of inducing cell death. In conclusion, our study demonstrates the promising therapeutic benefits of CBD and THC isolated from the Lebanese C. sativa plant on breast cancer cells in vitro. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
23. Dexmedetomidine ameliorates acute kidney injury by regulating mitochondrial dynamics via the α2-AR/SIRT1/PGC-1α pathway activation in rats.
- Author
-
Zhang, Shuai, Feng, Xiujing, Yang, Guiyan, Tan, Haoyang, Cheng, Xin, Tang, Qichao, Yang, Haotian, Zhao, Yuan, Ding, Xuanpan, Li, Siyao, Dou, Xinyi, Li, Junfeng, Kang, Huijie, Li, Xingxing, Ji, Yaxin, Hou, Qingdian, An, Qiuyue, Fang, Hao, and Fan, Honggang
- Abstract
Background: Sepsis-associated acute kidney injury (AKI) is a serious complication of systemic infection with high morbidity and mortality in patients. However, no effective drugs are available for AKI treatment. Dexmedetomidine (DEX) is an alpha 2 adrenal receptor agonist with antioxidant and anti-apoptotic effects. This study aimed to investigate the therapeutic effects of DEX on sepsis-associated AKI and to elucidate the role of mitochondrial dynamics during this process. Methods: A lipopolysaccharide (LPS)-induced AKI rat model and an NRK-52E cell model were used in the study. This study investigated the effects of DEX on sepsis-associated AKI and the molecular mechanisms using histologic assessment, biochemical analyses, ultrastructural observation, western blotting, immunofluorescence, immunohistochemistry, qRT-PCR, flow cytometry, and si-mRNA transfection. Results: In rats, the results showed that administration of DEX protected kidney structure and function from LPS-induced septic AKI. In addition, we found that DEX upregulated the α2-AR/SIRT1/PGC-1α pathway, protected mitochondrial structure and function, and decreased oxidative stress and apoptosis compared to the LPS group. In NRK-52E cells, DEX regulated the mitochondrial dynamic balance by preventing intracellular Ca2+ overloading and activating CaMKII. Conclusions: DEX ameliorated septic AKI by reducing oxidative stress and apoptosis in addition to modulating mitochondrial dynamics via upregulation of the α2-AR/SIRT1/PGC-1α pathway. This is a confirmatory study about DEX pre-treatment to ameliorate septic AKI. Our research reveals a novel mechanistic molecular pathway by which DEX provides nephroprotection. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
24. Role of layilin in regulating mitochondria-mediated apoptosis: a study on B cell lymphoma (BCL)-2 family proteins.
- Author
-
Arito, Mitsumi, Tsutiya, Atsuhiro, Sato, Masaaki, Omoteyama, Kazuki, Sato, Toshiyuki, Motonaga, Yusei, Suematsu, Naoya, Kurokawa, Manae S., and Kato, Tomohiro
- Abstract
Background: Malignant gliomas exhibit rapid tumor progression and resistance to treatment, leading to high lethality. One of the causes is the reduced progression of apoptosis in glioma cells. Layilin is a type 1 transmembrane protein with a C-type lectin motif in its extracellular domain. We previously reported that layilin is mainly localized to mitochondria or their close proximity and that layilin is essential for maintaining of the fragmented type of mitochondria. This study investigates the effects of layilin on mitochondria-mediated apoptosis, focusing on B cell lymphoma (BCL)-2 family proteins in a glioma cell line of A172 cells. Results: We compared the levels of pro-apoptotic BCL-2 family proteins of BAD, BAK, BAX, and BIM and anti-apoptotic BCL-2 family proteins of BCL-2 and BCL-XL between layilin- knockdown (KD) cells and control cells using western blot. The protein levels of BAD were significantly smaller in layilin-KD cells than in control cells, while those of BCL-2 were significantly larger. We then compared the mitochondrial membrane potential (ΔΨm) under p-trifluoromethoxyphenyl hydrazone (FCCP)-treated conditions using MT-1 staining. In layilin-KD cells, ΔΨm was significantly larger and FCCP-induced ΔΨm reduction was significantly lower than in control cells. Furthermore, we examined the levels of cell membrane-bound Annexin V and DNA-bound propidium idodide (PI) in layilin-KD cells with/without staurosporine (STS) treatment. Layilin-KD significantly decreased levels of cell membrane-bound Annexin V with/without STS treatment. On the other hand, PI levels were not changed by layilin-KD. We also investigated the amounts of the active caspase (CASP)-3, CASP-6, CASP-7, and poly (ADP-ribose) polymerase-1 (PARP1, cleaved form), as well as DNA fragmentation in layilin-KD cells under apoptotic conditions induced by STS, using western blot and the DNA ladder method, respectively. Under STS-treated conditions, the amounts of active CASP-3, CASP-7, and poly (ADP-ribose) PARP1 were significantly smaller in layilin-KD cells than in control cells. Accordingly, DNA fragmentation was significantly suppressed in layilin-KD cells compared to control cells under STS-treated conditions. Conclusion: This study demonstrates that layilin contributes to ΔΨm reduction to promote apoptosis by up-regulating BAD and down-regulating BCL-2 in glioma cells. Our data elucidates a new function of layilin: regulation of mitochondria-mediated apoptosis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
25. ETFDH mutation involves excessive apoptosis and neurite outgrowth defect via Bcl2 pathway.
- Author
-
Lin, Chuang-Yu, Liang, Wen-Chen, Yu, Yi-Chen, Chang, Shin-Cheng, Lai, Ming-Chi, and Jong, Yuh-Jyh
- Abstract
The most common mutation in southern Chinese individuals with late-onset multiple acyl-coenzyme A dehydrogenase deficiency (MADD; a fatty acid metabolism disorder) is c.250G > A (p.Ala84Thr) in the electron transfer flavoprotein dehydrogenase gene (ETFDH). Various phenotypes, including episodic weakness or rhabdomyolysis, exercise intolerance, and peripheral neuropathy, have been reported in both muscular and neuronal contexts. Our cellular models of MADD exhibit neurite growth defects and excessive apoptosis. Given that axonal degeneration and neuronal apoptosis may be regulated by B-cell lymphoma (BCL)-2 family proteins and mitochondrial outer membrane permeabilization through the activation of proapoptotic molecules, we measured the expression levels of proapoptotic BCL-2 family proteins (e.g., BCL-2-associated X protein and p53-upregulated modulator of apoptosis), cytochrome c, caspase-3, and caspase-9 in NSC-34 cells carrying the most common ETFDH mutation. The levels of these proteins were higher in the mutant cells than in the wide-type cells. Subsequent treatment of the mutant cells with coenzyme Q10 downregulated activated protein expression and mitigated neurite growth defects. These results suggest that the activation of the BCL-2/mitochondrial outer membrane permeabilization/apoptosis pathway promotes apoptosis in cellular models of MADD and that coenzyme Q10 can reverse this effect. Our findings aid the development of novel therapeutic strategies for reducing axonal degeneration and neuronal apoptosis in MADD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
26. Autophagy and autophagic cell death in sepsis: friend or foe?
- Author
-
Iba, Toshiaki, Helms, Julie, Maier, Cheryl L., Ferrer, Ricard, and Levy, Jerrold H.
- Abstract
In sepsis, inflammation, and nutrient deficiencies endanger cellular homeostasis and survival. Autophagy is primarily a mechanism of cellular survival under fasting conditions. However, autophagy-dependent cell death, known as autophagic cell death, is proinflammatory and can exacerbate sepsis. Autophagy also regulates various types of non-inflammatory and inflammatory cell deaths. Non-inflammatory apoptosis tends to suppress inflammation, however, inflammatory necroptosis, pyroptosis, ferroptosis, and autophagic cell death lead to the release of inflammatory cytokines and damage-associated molecular patterns (DAMPs) and amplify inflammation. The selection of cell death mechanisms is complex and often involves a mixture of various styles. Similarly, protective autophagy and lethal autophagy may be triggered simultaneously in cells. How cells balance the regulatory mechanisms of these processes is an area of interest that is still under investigation. Therapies aimed at modulating autophagy are considered promising. Enhancing autophagy helps clear and recycle damaged organelles and reduce the burden of inflammatory processes while inhibiting excessive autophagy, which could prevent autophagic cell death. In this review, we introduce recent advances in research and the complex regulatory system of autophagy in sepsis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
27. <italic>Ante-mortem</italic> glutathione peroxidase 4 inhibition by RSL3 affects post-mortem meat quality in broiler chickens.
- Author
-
Nakanishi, T., Uchiyama, T., Uchida, M., Erickson, L., and Kawahara, S.
- Subjects
- *
GLUTATHIONE peroxidase , *MEAT quality , *APOPTOSIS , *BROILER chickens , *SKELETAL muscle , *BREAST , *POSTMORTEM changes - Abstract
1. This study investigated the role of glutathione peroxidase 4 (GPX4), a key regulator of ferroptosis, a form of programmed cell death, in muscle biochemistry and meat quality, utilising broiler chickens whose
ante-mortem GPX4 activity was inhibited pharmacologically.2. Male broilers were divided into two groups, each receivingante-mortem administration of the GPX4 inhibitor, Ras-selective lethal 3 (RSL3), or a vehicle only. After slaughter, breast muscles were collected and stored for 48 h. The expressions of ferroptosis-related genes, glutathione levels, pH, colour and water-holding capacity were evaluated at multiple time points during the storage period.3. The RSL3 treatment decreased the expression ofGPX4 and ferritin heavy chain 1, which are negative regulators of ferroptosis, while it increased the expression of a ferroptosis accelerator, acyl-CoA synthetase long chain family member 4. The ratio of reduced to oxidised glutathione was significantly decreased in the RSL3 group. The RSL3 treatment decelerated post-mortem pH decline and colour changes, such as a decrease in L* and an increase in a* were observed in the RSL3 group. In addition, the RSL3 group showed increased levels of water-holding capacity.4. These findings suggested thatante-mortem GPX4 activity plays a role in determining meat quality, implying the possible involvement of ferroptosis in the mechanism by which skeletal muscle is converted after slaughter into meat that is eaten. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
28. Histone deacetylase inhibitors for leukemia treatment: current status and future directions.
- Author
-
Hosseini, Mohammad-Salar, Sanaat, Zohreh, Akbarzadeh, Mohammad Amin, Vaez-Gharamaleki, Yosra, and Akbarzadeh, Mahsa
- Abstract
Leukemia remains a major therapeutic challenge in clinical oncology. Despite significant advancements in treatment modalities, leukemia remains a significant cause of morbidity and mortality worldwide, as the current conventional therapies are accompanied by life-limiting adverse effects and a high risk of disease relapse. Histone deacetylase inhibitors have emerged as a promising group of antineoplastic agents due to their ability to modulate gene expression epigenetically. In this review, we explore these agents, their mechanisms of action, pharmacokinetics, safety and clinical efficacy, monotherapy and combination therapy strategies, and clinical challenges associated with histone deacetylase inhibitors in leukemia treatment, along with the latest evidence and ongoing studies in the field. In addition, we discuss future directions to optimize the therapeutic potential of these agents. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
29. Increased Lipocalin 2 detected by RNA sequencing regulates apoptosis and ferroptosis in COPD.
- Author
-
Wang, Ruiying, Xu, Jianying, Wei, Shuang, and Liu, Xiansheng
- Abstract
Background: Chronic obstructive pulmonary disease (COPD) is a complex respiratory condition influenced by environmental and genetic factors. Using next-generation sequencing, we aimed to identify dysregulated genes and potential therapeutic targets for COPD. Methods: Peripheral blood leukocyte RNA profiles from COPD patients and healthy controls were analyzed using next-generation sequencing. Key genes involved in COPD pathogenesis were identified through protein–protein interaction network analysis. In vitro, bronchial epithelial cells treated with cigarette smoke extract (CSE) were used to study the effects on gene expression, cell viability, apoptosis, and ferroptosis. Additionally, Lipocalin 2 (LCN2) inhibition experiments were conducted to elucidate its role in COPD-related cellular processes. Results: Analysis of RNA profiles revealed consistent downregulation of 17 genes and upregulation of 21 genes across all COPD groups. Among these, Cathelicidin Antimicrobial Peptide(CAMP), Defensin Alpha 4(DEFA4), Neutrophil Elastase(ELANE), LCN2 and Lactotransferrin(LTF) were identified as potentially important players in COPD pathogenesis. Particularly, LCN2 exhibited a close association with COPD and was found to be involved in cellular processes. In vitro experiments demonstrated that CSE treatment significantly increased LCN2 expression in bronchial epithelial cells in a concentration-dependent manner. Moreover, CSE-induced apoptosis and ferroptosis were observed, along with alterations in cell viability, Glutathione content, Fe2 + accumulation, ROS: Reactive Oxygen Species and Malondialdehyde levels, Lactate Dehydrogenase(LDH) release and Glutathione Peroxidase 4(GPX4) expression. Inhibition of LCN2 expression partially reversed these effects, indicating the pivotal role of LCN2 in COPD-related cellular processes. Conclusion: Our study identified six candidate genes: CAMP, DEFA4, ELANE, LCN2, and LTF were upregulated, HSPA1B was downregulated. Notably, LCN2 emerges as a significant biomarker in COPD pathogenesis, exerting its effects by promoting apoptosis and ferroptosis in bronchial epithelial cells. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
30. Exocyclic and Linker Editing of Lys63‐linked Ubiquitin Chains Modulators Specifically Inhibits Non‐homologous End‐joining Repair.
- Author
-
Saha, Abhishek, Bishara, Laila A., Saed, Yakop, Vamisetti, Ganga B., Mandal, Shaswati, Suga, Hiroaki, Ayoub, Nabieh, and Brik, Ashraf
- Subjects
- *
CYCLIC peptides , *HOMOLOGOUS recombination , *CELL permeability , *DNA repair , *PEPTIDES , *DOUBLE-strand DNA breaks - Abstract
Despite the great advances in discovering cyclic peptides against protein targets, their reduced aqueous solubility, cell permeability, and activity of the cyclic peptide restrict its utilization in advanced biological research and therapeutic applications. Here we report on a novel approach of structural alternation of the exocyclic and linker parts that led to a new derivative with significantly improved cell activity allowing us to dissect its mode of action in detail. We have identified an effective cyclic peptide (CP7) that induces approximately a 9‐fold increase in DNA damage accumulation and a remarkable increase in apoptotic cancer cell death compared to the reported molecule. Notably, treating cells with CP7 leads to a dramatic decrease in the efficiency of non‐homologous end joining (NHEJ) repair of DNA double‐strand breaks (DSBs), which is accompanied by an increase in homologous recombination (HR) repair. Interestingly, treating BRCA1‐deficient cells with CP7 restores HR integrity, which is accompanied by increased resistance to CP7. Additionally, CP7 treatment increases the sensitivity of cancer cells to ionizing radiation. Collectively, our findings demonstrate that CP7 is a selective inhibitor of NHEJ, offering a potential strategy to enhance the effectiveness of radiation therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
31. Effects of Resveratrol on Nonmelanoma Skin Cancer (NMSC): A Comprehensive Review.
- Author
-
Zamanian, Mohammad Yasin, Shahbazi, Taha, Kazmi, Syeda Wajida, Hussien, Beneen M., Sharma, Abhishek, Qasim, Maytham T., Hjazi, Ahmed, Sapaev, Ibrohim B., Nouri Danesh, Ayda, Taheri, Niloofar, and Golmohammadi, Maryam
- Subjects
- *
BASAL cell carcinoma , *SKIN cancer , *TREATMENT effectiveness , *REACTIVE oxygen species , *SQUAMOUS cell carcinoma , *LIPOSOMES - Abstract
ABSTRACT Nonmelanoma skin cancer (NMSC) represents the most prevalent form of skin cancer globally, with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) being the most common types. The search for effective chemopreventive and therapeutic agents has led to the exploration of natural compounds, among which resveratrol (RES), a polyphenolic phytoalexin found in grapes, berries, peanuts, and red wine, has garnered significant attention. This comprehensive review aims to elucidate the effects of RES on NMSC, focusing on its mechanisms of action, efficacy in preclinical studies, and potential as a chemopreventive and therapeutic agent. RES exhibits promising chemopreventive and antineoplastic capabilities against NMSC through various mechanisms, including the induction of apoptosis, inhibition of cell proliferation, modulation of oxidative stress, and anti‐inflammatory activities. Studies have demonstrated that RES can significantly enhance the effectiveness of traditional chemotherapeutic agents, such as 5‐fluorouracil (5‐FU), by inhibiting cellular proliferation and inducing apoptosis in cancerous cells. Furthermore, resveratrol's antioxidant properties may mitigate the impact of reactive oxygen species (ROS) triggered by UV exposure, thus reducing DNA damage and mutations associated with skin cancer development. In vitro and in vivo experiments have shown that RES can effectively hinder the growth and spread of various tumor cell types, including human cutaneous SCC A431 cells, and induce apoptosis. The development of advanced delivery systems, such as nanostructured lipid carriers and liposomes, has been recognized for their potential to enhance the therapeutic effects of RES, particularly its anticancer properties. In conclusion, RES presents a viable candidate for the prevention and treatment of NMSC, owing to its multifaceted mechanisms of action, including its ability to regulate oxidative stress, trigger apoptosis, and inhibit proliferation. However, further clinical studies are required to fully understand its effectiveness and safety in humans, as well as to optimize delivery methods for improved bioavailability and therapeutic outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
32. Oncolytic avian reovirus-sensitized tumor infiltrating CD8+ T cells triggering immunogenic apoptosis in gastric cancer.
- Author
-
Wu, Yi-Ying, Wu, Feng-Hsu, Chen, I-Chun, Liao, Tsai-Ling, Munir, Muhammad, and Liu, Hung-Jen
- Subjects
- *
MONONUCLEAR leukocytes , *TUMOR-infiltrating immune cells , *LACTATE dehydrogenase , *STOMACH cancer , *CELLULAR signal transduction - Abstract
Background: Gastric cancer (GC) is a leading malignant disease in numerous countries, including Taiwan with limited therapeutic options. Animal viruses including oncolytic avian reovirus (ARV) have the possibility to avoid pre-existing immunity in humans, while being safe and immunostimulatory. Here, we provide a novel insight into oncolytic ARV and UV-ARV-sensitized patient's peripheral blood mononuclear cells (P-PBMCs) and tumor infiltrating lymphocytes (TILs) killing primary GC (PGC) cells through the surface TLR3 and TRAIL/DR4/DR5 immunogenic apoptosis pathway. Methods: We conducted a comprehensive study to reveal whether ARV- or UV-inactivated ARV (UV-ARV)-modulated P-PBMCs or TILs killing ARV- and UV-ARV-sensitized AGS cells and PGC cells derived from clinical patients and to investigate the regulation of surface TLR3 receptor and upstream signaling pathways. Apoptosis analysis by flow cytometry and Western blot, suppression of signal pathway by specific inhibitors, in situ proximity ligation assay (PLA), time-resolved flurometry and lactate dehydrogenase (LDH) cytotoxicity assays, and an in vitro co-culture model were established to study the interplay between ARV- and UV-ARV-sensitized P-PBMCs and TILs to kill PGC cells and their upstream pathways. Results: Our results reveal that increased levels of DR4 and DR5 were observed in ARV and UV-ARV sensitized PGC cells through the TLR3/p38/p53 signaling pathway. Importantly, we found that the σC protein of ARV or UV-ARV interacted with surface TLR3 of CD8+ TILs, thereby triggering the TLR3/NF-κB/IFN-γ/TRAIL signaling pathway which induces immunogenic apoptosis of PGC cells. This study sheds further light on the molecular basis behind ARV oncolysis and facilitates the ARV or UV-ARV as a cancer therapeutic. Conclusions: The study provides novel insights into ARV- or UV-ARV-sensitized P-PBMCs and CD8+ TILs to kill PGC cells through the immunogenic apoptosis pathway. We conclude that P-PBMCs can easily be obtained from GC patients and provide a rich source as TILs to kill PGC cells. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
33. Botanical Sources, Pharmacokinetics, and Therapeutic Efficacy of Palmatine and Its Derivatives in the Management of Cancer: A Comprehensive Mechanistic Analysis.
- Author
-
Jahan Oni, Most. Israt, Bhuia, Md. Shimul, Chowdhury, Raihan, Sheikh, Salehin, Munshi, Md. Hanif, Hasan, Md. Sakib Al, Islam, Muhammad Torequl, and Restivo, Ignazio
- Subjects
- *
CELL migration inhibition , *ISOQUINOLINE alkaloids , *CELL cycle , *HEPATOCELLULAR carcinoma , *LIVER cancer , *BREAST - Abstract
Natural compounds and their derivatives have been identified as valuable sources of therapeutic ingredients for cancer treatment. The naturally occurring phytochemical palmatine (isoquinoline alkaloid) is extracted from plant parts (rhizomes, roots, stems, stem barks, and others) and has protective effects including antioxidant, anti‐inflammatory, and anticancer. This study aims to summarize the anticancer potential of palmatine and its derivatives in the treatment of numerous types of cancer with molecular mechanisms. We also include the pharmacokinetic features, botanical origin, and toxicological characteristics of palmatine and its derivatives. For this, data have been collected from plausible different electronic databases, including PubMed, Google Scholar, PubChem, Science Direct, Web of Science, Scopus, Springer Link, and Wiley Online. The findings demonstrate that palmatine and its derivatives have a protective anticancer effect against a variety of cancers, including breast, colorectal, gastric, ovarian, prostate, pancreatic, skin, hepatocellular cancer, and mammary gland tumors. They provoke their anticancer properties against various cancer cell lines via modifying molecular mechanisms like induction of oxidative stress, cytotoxicity, apoptosis, inhibition of cell invasion and migration, arresting the cell cycle at the S phase, antiproliferative, and antiangiogenic effects. It is suggested that palmatine and its derivatives may be a good option in the development of novel drugs for cancer therapy in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
34. Therapeutic effect of berberine against 5-fluorouracil induced ovarian toxicity in rats.
- Author
-
Demir, Selim, Turkmen Alemdar, Nihal, Kucuk, Hatice, Ayazoglu Demir, Elif, Menteşe, Ahmet, and Aliyazıcıoğlu, Yuksel
- Subjects
- *
OXIDANT status , *TUMOR necrosis factors , *OXIDATIVE stress , *OVARIES , *SUPEROXIDE dismutase , *BERBERINE - Abstract
Berberine (BER) is a naturally occurring alkaloid with a multitude of beneficial effects on human health. Although it is one of the most studied phytochemicals, its curative effect against ovarian damage caused by 5-fluorouracil (5-FU) has not been demonstrated to date. The aim of this study was to investigate the possible protective effect of BER against 5-FU-induced ovotoxicity, focusing on its ability to attenuate oxidative stress, inflammation and apoptosis. The 30 female rats were randomly divided into five groups: Control, BER (2 mg/kg), 5-FU (100 mg/kg), 5-FU+BER (1 mg/kg) and 5-FU+BER (2 mg/kg). The levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT), 8-hydroxy-2’-deoxyguanosine (8-OHdG), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and caspase-3 were determined using spectrophotometric methods. In addition, ovarian samples were evaluated histopathologically using hematoxylin&eosin staining method. The MDA, TOS, 8-OHdG, IL-6, TNF-α and caspase-3 levels significantly increased by 5-FU administration. Also, we found that 5-FU significantly decreased TAS, SOD and CAT levels. Treatments with BER significantly attenuated the 5-FU-induced ovarian damage via increasing the antioxidant capacity and reducing the oxidative stress, inflammation and apoptosis in a dose-dependent manner. Moreover, the ovoprotective effect of BER was also confirmed by histopathological evaluation. BER may be evaluated as a potential candidate molecule to reduce 5-FU-induced ovarian toxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
35. Transcriptome analysis reveals a role of FOXO3 in antileukemia/lymphoma properties of panduratin A.
- Author
-
Phuagkhaopong, Suttinee, Janpattanapichai, Jiranan, Sirirak, Noppavut, Khemawoot, Phisit, Vivithanaporn, Pornpun, and Suknuntha, Kran
- Subjects
- *
TRANSCRIPTION factors , *CELLULAR aging , *INHIBITION of cellular proliferation , *B cells , *CANCER cells , *FORKHEAD transcription factors - Abstract
Boesenbergia rotunda, commonly known as fingerroot, is a medicinal and culinary plant native to the Indochina Peninsula. We found that panduratin A (Pan-A), one of the compounds present in the rhizome extract of fingerroot, inhibited cell proliferation, induced apoptosis, and promoted cell cycle arrest at G0/G1 phase in multiple hematologic malignant cell lines including leukemia and lymphoma lines. Pan-A inhibited these activities in leukemia and lymphoma cells in a concentration-dependent manner. High-throughput transcriptome analysis indicated that Pan-A is involved in the cell cycle, cellular senescence, apoptosis, and multiple canonical signaling pathways in lymphoma cells. The Forkhead box O (FOXO) transcription factor family was identified as a potential target of Pan-A. Western blot showed elevated caspase 7 and cPARP/PARP in the B-cell lymphoma cells after treatment with Pan-A. The inhibitory effects were accompanied by stimulation of Akt signaling and phosphorylation of FOXO3. Immunohistochemistry of tissues from patients with B-cell lymphoma revealed detectable levels of FOXO3 protein specifically in neoplastic B cells. Overall, our results highlight FOXO3 as a player underlying antileukemia/lymphoma effects of Pan-A. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
36. Porphyromonas gingivalis Promotes Oral Squamous Cell Carcinoma Progression by Modulating Autophagy.
- Author
-
Yuan, Keyong, Xu, Shengming, Liu, Guanglong, Han, Yong, Hu, Jingzhou, Zhang, Wuchang, Zhang, Zhiyuan, Liu, Liu, Huang, Zhengwei, Zhu, Yu, and Liu, Shuli
- Subjects
- *
SQUAMOUS cell carcinoma , *PORPHYROMONAS gingivalis , *TUMOR growth , *CANCER invasiveness , *AUTOPHAGY - Abstract
ABSTRACT Objectives Materials and Methods Results Conclusion Porphyromonas gingivalis (P. gingivalis) is a keystone periodontal pathogen associated with various gastro‐intestinal tract cancers. However, whether P. gingivalis can promote oral squamous cell carcinoma (OSCC) and the underlying mechanism associated with such promotion remain unclear.In this study, OSCC xenograft models were used to evaluate the effects of P. gingivalis on tumor progression. The functional studies were done on several OSCC cell lines in vitro. P. gingivalis‐specific 16S rRNA fluorescent in situ hybridization (FISH) was used to test its prevalence in clinical samples.We found that P. gingivalis increased tumor volume and tumor growth in OSCC nude models. Functional studies demonstrated that P. gingivalis inhibited the apoptosis of OSCC cells by promoting cellular autophagy. P. gingivalis was more prevalent in FISH samples from patients with OSCC than from patients with leukoplakia or healthy subjects (70% vs. 47.2% vs. 33.3%, p = 0.045 and p < 0.001, respectively).These data suggest that P. gingivalis plays an accelerating role in OSCC progression and contributes to OSCC by enhancing the autophagy pathway to reduce carcinoma apoptosis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
37. Identification and characterization of chicken TRIM45 and its role as a negative regulator of ALV-J replication in vitro.
- Author
-
Wang, Jiaxing, Wang, Qiangzhou, Ping, Yuyu, Huang, Xuan, Yang, Ting, Bi, Yulin, Chang, Guobin, and Chen, Shihao
- Subjects
- *
GENETIC overexpression , *GENE expression , *AVIAN leukosis , *CHICKENS , *GENE silencing , *CHICKEN diseases - Abstract
Avian leukosis virus subgroup J (ALV-J) is an alpharetrovirus that infects chickens, causing immunosuppression and a decrease in production performance, leading to substantial economic losses in the poultry industry. ALV-J is also well-known for its oncogenic properties, inducing tumors such as myelomas and hemangiomas in infected chickens. TRIM45 has been identified as a potential tumor suppressor, however, the relationship between TRIM45 expression and ALV-J infection remains to be elucidated.This study aimed to dissect the molecular characteristics of the chicken TRIM45 gene and its modulation during ALV-J infection, as well as its influence on viral replication. We found that the chicken TRIM45 RING domain is significantly different from that of humans and other mammals. TRIM45 is expressed in all chicken tissues, with the highest levels in the heart. Subcellular localization studies indicated a cytoplasmic distribution of TRIM45, forming aggregates within cells. Our findings demonstrate that ALV-J infection significantly upregulates TRIM45 expression in DF-1 cells. To assess the functional role of TRIM45 in ALV-J replication, we employed both gene silencing and overexpression strategies. Strikingly, the overexpression of TRIM45, including a mutant lacking the RING domain, was found to markedly suppress ALV-J replication. In contrast, TRIM45 knockdown via siRNA resulted in an enhanced viral replication, highlighting the importance of TRIM45 limiting ALV-J replication. Mechanistically, overexpression of TRIM45 induces apoptosis in infected cells, independent of its RING domain function. In conclusion, our study demonstrates that chicken TRIM45 acts as a negative regulator of ALV-J replication in vitro by promoting apoptosis in infected cells. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
38. The expression of VDACs and Bcl2 family genes in pituitary adenomas: clinical correlations and postsurgical outcomes.
- Author
-
Facundo, AN, Magalhães, M., Nascimento, GC, Azulay, RS, Santos, RM, Freitas, LA, Nascimento, AGPAC, Rodrigues, VP, Santos, WC, Beckman, AMGS, Abreu, JMF, Silva, RP, Carneiro, EL, Oliveira Neto, CP, Gil da Costa, RM, Corcoy, R., Mato, E., and Faria, MA
- Subjects
GENE expression ,CUSHING'S syndrome ,PITUITARY tumors ,BAX protein ,DISEASE relapse - Abstract
Introduction: Pituitary adenomas (PAs) are benign tumors with high prevalence and, occasionally, aggressive course. The tumorigenesis of these lesions is not completely understood at the molecular level. BAK1 and BAX proteins play fundamental roles in apoptosis and seem to interact with VDAC proteins, whose expressions have been markedly altered in cancer, impacting their prognosis. Objective: to evaluate the gene expression of VDAC1, VDAC2, BAK1 and BAX and their association with clinical and imaging characteristics in PA. Methods: Clinical-epidemiological data were collected from 117 tumor samples from patients affected by PA. Invasiveness was assessed by the Knosp scale. Gene expression was examined by real-time PCR. Relative expression analysis was performed by 2^(-DDCt) method. Results: The sample was mainly composed of women (69/117 -- 57.2%). Tumor subtypes observed were Non-Functioning (NF) (73/117 -- 62.4%), Acromegaly (24/117 -- 20.5%) and Cushing's Disease (CD) (20/117 -- 17.1%). Compared to normal tissue, there was a significant reduction in VDAC1 expression in the Acromegaly (p=0.029) and NF (p=0.002) groups. BAX expression was lower in all groups (p <0.001; p=0.007; P =0.005). No difference was found in VDAC2 and BAK1 expression, compared to normal pituitary. Overexpression of VDAC2 occurred in PAs with post-surgical regrowth (p=0.042). A strongly negative correlation was observed in BAX and BAK1 expression in CD. Conclusion: The results indicated that downregulations of VDAC1 and BAX may be related to resistance to apoptosis. In contrast, overexpression of VDAC2 in regrowing PAs suggests an antiapoptotic role for this gene. In summary, the genes evaluated might be involved in the biopathology of PAs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
39. A disulfidptosis-related lncRNA signature for analyzing tumor microenvironment and clinical prognosis in hepatocellular carcinoma.
- Author
-
Haishui Zheng, Jigan Cheng, Ziyun Zhuang, Duguang Li, Jing Yang, Fan Yuan, Xiaoxiao Fan, and Xiaolong Liu
- Subjects
LINCRNA ,APOPTOSIS ,CANCER prognosis ,DISEASE risk factors ,TREATMENT effectiveness - Abstract
Introduction: Disulfidptosis is a recently identified form of non-apoptotic programmed cell death which distinguishes itself from classical cell death pathways. However, the prognostic implications of disulfidptosis-related long non-coding RNAs (DRLs) and their underlying mechanisms in hepatocellular carcinoma (HCC) remain largely unexplored. Methods: In this study, we leveraged RNA-sequencing data and clinical information of HCC patients from the TCGA database. Through expression correlation and prognostic correlation analyses, we identified a set of topperforming long non-coding RNAs. Subsequently, a 5-DRLs predictive signature was established by conducting a Lasso regression analysis. Results: This signature effectively stratified patients into high- and low-risk groups, revealing notable differences in survival outcomes. Further validation through univariate and multivariate Cox regression analyses confirmed that the risk score derived from our signature independently predicted the prognosis of HCC patients. Moreover, we observed significant disparities in immune cell infiltration and tumor mutation burden (TMB) between the two risk groups, shedding light on the potential connection between immune-related mechanisms and disulfidptosis. Notably, the signature also exhibited predictive value in the context of chemotherapeutic drug sensitivity and immunotherapy efficacy for HCC patients. Finally, we performed experimental validation at both cellular and patient levels and successfully induced a disulfidptosis phenotype in HCC cells. Discussion: In general, this multifaceted approach provides a comprehensive overview of DRLs profiles in HCC, culminating in the establishment of a novel risk signature that holds promise for predicting prognosis and therapy outcomes of HCC patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
40. Exploring the potential of MFG-E8 in neurodegenerative diseases.
- Author
-
Li, Dan, Rongchun, Wang, Lu, Weihong, and Ma, Ying
- Abstract
Abstract\nHIGHLIGHTSMilk fat globule-epidermal growth factor 8 (MFG-E8) is a multifunctional glycoprotein regulating intercellular interactions in various biological and pathological processes. This review summarizes the effects and mechanisms of MFG-E8 in neurodegenerative diseases (NDDs), emphasizing its roles in inflammation, apoptosis, and oxidative stress. In this review, will also explore the potential of MFG-E8 as a diagnostic biomarker and its therapeutic applications in neurodegenerative disorders. Recent studies have revealed intriguing characteristics of using MFG-E8 as a potential drug for treating various brain disorders. While the discovery, origin, expression, and physiological functions of MFG-E8 in various organs and tissues are well defined, its role in the brain remains less understood. This is particularly true for NDDs, indicating unmet medical needs. Elucidating its role in the brain could position MFG-E8 as a potential treatment for NDDs.The expression and regulation of MFG-E8 in neurodegenerative diseases.The role of MFG-E8 in the mechanisms of neurodegenerative diseases.Potential application challenges and strategies for MFG-E8 as a therapeutic target.The expression and regulation of MFG-E8 in neurodegenerative diseases.The role of MFG-E8 in the mechanisms of neurodegenerative diseases.Potential application challenges and strategies for MFG-E8 as a therapeutic target. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
41. From virus to cancer: Epstein–Barr virus miRNA connection in Burkitt's lymphoma.
- Author
-
Jalilian, Shahram and Bastani, Mohammad-Navid
- Subjects
- *
MICROBIAL virulence , *DIFFUSION of innovations , *MICRORNA , *APOPTOSIS , *CELL proliferation , *TUMOR markers , *CELLULAR signal transduction , *EPSTEIN-Barr virus , *B cell lymphoma - Abstract
In Burkitt's lymphoma (BL), Epstein–Barr virus-encoded microRNAs (EBV miRNAs) are emerging as crucial regulatory agents that impact cellular and viral gene regulation. This review investigates the multifaceted functions of EBV miRNAs in the pathogenesis of Burkitt lymphoma. EBV miRNAs regulate several cellular processes that are essential for BL development, such as apoptosis, immune evasion, and cellular proliferation. These small, non-coding RNAs target both viral and host mRNAs, finely adjusting the cellular environment to favor oncogenesis. Prominent miRNAs, such as BART (BamHI-A rightward transcript) and BHRF1 (BamHI fragment H rightward open reading frame 1), are emphasized for their roles in tumor growth and immune regulation. For example, BART miRNAs prevent apoptosis by suppressing pro-apoptotic proteins, whereas BHRF1 miRNAs promote viral latency and immunological evasion. Understanding the intricate connections among EBV miRNAs and their targets illuminates BL pathogenesis and suggests novel treatment approaches. Targeting EBV miRNAs or their specific pathways offers a feasible option for developing innovative therapies that aim to disrupt the carcinogenic processes initiated by these viral components. future studies should focus on precisely mapping miRNA‒target networks and developing miRNA-based diagnostic and therapeutic tools. This comprehensive article highlights the importance of EBV miRNAs in Burkitt lymphoma, indicating their potential as biomarkers and targets for innovative treatment strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
42. Protective effect of fructooligosaccharide against oxidative stress and apoptosis induced by Aeromonas hydrophila in Megalobrama amblycephala.
- Author
-
Zhang, Chunnuan, Jiang, Dongxue, Shi, Huajuan, Zhang, Cheng, Yang, Feng, Qi, Qian, and Xu, Ruiyi
- Subjects
- *
AEROMONAS hydrophila , *FOS oncogenes , *FRUCTOOLIGOSACCHARIDES , *CASPASES , *SEBASTES marinus - Abstract
This research aimed to investigate the effects of dietary fructooligosaccharides (FOS) on attenuating the Aeromonas hydrophila (A. hydrophila)-induced oxidative stress and apoptosis in blunt snout bream Megalobrama amblycephala. Fish were divided into three groups as follows: C1 (Control), T1 (A. hydrophila), and T2 (A. hydrophila + 4 g/kg FOS). The results showed that the activities of antioxidant enzymes increased, the liver morphology had disorderly arrangement, and extensive cell necrosis occurred because of A. hydrophila-infection. While the dietary FOS improved the above-mentioned liver damage. Additionaly, FOS elevated mRNA levels of pro-apoptotic molecules, including caspase-8 and 9, and down-regulated mRNA levels of the anti-apoptotic molecule Bcl-2, which is triggered by A. hydrophila-infection. The transcriptome analysis showed that the oxidative stress-related DEGs pathways were activated in intestine of blunt snout bream by A. hydrophila-infection. The FOS-added group led to the enrichment of more pathways to health. Further WGCNA co-expression network analysis showed that the screened single genes were clustered into 49 modules. The two modules with the highest association to the five traits (10 hub genes) were chosen to build the network by combining the physiological and biochemical characteristic. In summary, this research offers a foundation for the exploring of A. hydrophila-restoration genes in dietary FOS, and also lays a theoretical foundation for aquaculture in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
43. Anticancer potentiality of Hottentotta saulcyi scorpion curd venom against breast cancer: an in vitro and in vivo study.
- Author
-
Nosouhian, Mahshid, Rastegari, Ali Asghar, Shahanipour, Kahin, Ahadi, Ali Mohammad, and Sajjadieh, Mohammadreza Sheikh
- Subjects
- *
SCORPION venom , *CYTOTOXINS , *ELECTRIC stimulation , *GENETIC transcription , *FLUORESCENCE microscopy , *VENOM - Abstract
Scorpion venom may include pharmacological substances that have the potential to provide benefits. Multiple scientific investigations have shown that particular scorpion venoms induce apoptosis and inhibit the development of cancerous cells. The present study investigated the potential anticancer properties of the crude venom derived from Hottentotta saulcyi (H. saulcyi) on both in vivo mice models and in vitro breast carcinoma cells. The venom of scorpions belonging to the species H. saulcyi was obtained with the application of electrical stimulation at voltages of 8 and 10 V. The determination of the Average Lethal Dose 50 (LD50) was conducted. The present work assessed the in vitro cytotoxicity and morphological characteristics of H. saulcyi venom using fluorescence microscopy, MTT assay, and flow cytometry assessment. Additionally, research was performed to assess the cytotoxic effects in vivo on a mouse model with breast cancer. The examination of MCF-7 cells treated with scorpion venom at a microscopic level revealed the existence of cells undergoing apoptosis. The venom of H. saulcyi has anticancer properties, as shown by the observation that MCF-7 cells had a 62.12% apoptotic rate when exposed to a dose of 1.47 mg/L. Based on the results obtained, it can be shown that the viability of MCF-7 cells has exhibited a substantial reduction (P < 0.01). Furthermore, the findings indicated that the venom of H. saulcyi resulted in a significant increase in the synthesis of TNF-α, IL-6, IL-10, TGF-β, and caspase (P < 0.05). The treatment groups administered with H. saulcyi venom exhibited a significant augmentation in the expression of proapoptotic genes compared to the control group of healthy individuals. The transcription of the BCL2 gene exhibited a statistically significant increase in the healthy control group compared to both the healthy venom-treated group (P < 0.05) and the malignant venom-treated group (P < 0.01). The crude venom of H. saulcyi has considerable promise in demonstrating anticancer properties. Further investigation may be warranted to explore the potential of using H. saulcyi crude venom as a medicinal platform for the prevention of breast cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
44. Synthesis, Reaction Mechanism, DNA Cleavage, and Antitumor Properties of Pyridazinedione‐Fused Enediynes.
- Author
-
Zhang, Houjun, Li, Xuejie, Cheng, Haonan, Pu, Fangxu, Zheng, Hongyu, Huang, Xiaohua, Ding, Yun, Lan, Jiaming, and Hu, Aiguo
- Subjects
- *
COMPUTATIONAL chemistry , *ELECTRON paramagnetic resonance , *APOPTOSIS , *DIFFERENTIAL scanning calorimetry , *ANTINEOPLASTIC antibiotics - Abstract
Natural enediyne antibiotics undergo thermally induced cycloaromatization under physiological conditions to generate highly reactive diradicals that effectively abstract hydrogen atoms from biomacromolecules like DNA, leading to DNA cleavage and inducing programmed cell death in tumor cells, exhibiting potent cytotoxicity and broad‐spectrum antitumor properties. In order to further explore promising synthetic analogues of natural enediynes, a 3,6‐pyridazinedione moiety was fused at the ene‐position, and 10 new enediyne compounds with different atoms at the propargylic positions were synthesized. Differential scanning calorimetry (DSC) and electron paramagnetic resonance results indicated that these enediynes exhibited a rather low onset temperature and the capability to generate radical species at physiological temperatures. Density functional theory (DFT) calculations demonstrated that the pyridazinedione moiety facilitates cascade rearrangement processes, thereby endowing the key cycloaromatization with a low energy barrier. The enediynes with propargylic oxygen exhibit strong DNA cleavage capabilities, and all pyridazinedione‐fused enediynes showed IC50 values in the range of several tens of micromolars against HeLa cells. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
45. Metformin suppresses metabolic dysfunction-associated fatty liver disease by ferroptosis and apoptosis via activation of oxidative stress.
- Author
-
Li, Zhiyu, Cui, Chao, Xu, Liang, Ding, Mingfeng, and Wang, Yinghui
- Subjects
- *
FATTY liver , *FREE fatty acids , *PHOSPHOLIPASE A2 , *REACTIVE oxygen species , *IRON metabolism - Abstract
Abstract\nKEY POLICY HIGHLIGHTSMetformin is known for its antioxidant properties and ability to ameliorate metabolic dysfunction-associated fatty liver disease (MAFLD) and is the focus of this study. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is linked to MAFLD risk. This study investigated the effects of metformin on ferroptosis in free fatty acid (FFA)-treated Huh7 hepatoma cells and its association with MAFLD risk. Using Western blot, immunofluorescence, and ELISA, this study revealed that FFA treatment led to increased intracellular fat and iron accumulation, heightened Lp-PLA2 expression, reduced levels of the cysteine transporter SLC7A11 and glutathione peroxidase 4 (GPX4), altered glutathione (GSH)/oxidized glutathione (GSSG) ratios, generation of reactive oxygen species (ROS), and initiation of lipid peroxidation, which ultimately resulted in cell ferroptosis. Importantly, metformin reversed FFA-induced iron accumulation, and this effect was attenuated by ferrostatin-1 but enhanced by erastin, RSL3, and si-GPX4. Additionally, metformin activated antioxidant and antiapoptotic mechanisms, which reduced lipid peroxidation and suppressed Lp-PLA2 expression in FFA-treated Huh7 cells. In conclusion, our findings indicate that metformin may protect against MAFLD by inhibiting iron accumulation and Lp-PLA2 expression through the ROS, ferroptosis, and apoptosis signaling pathways. This study highlights potential therapeutic strategies for managing MAFLD-related risks and emphasizes the diverse roles of metformin in maintaining hepatocyte balance.Metformin lowered Lp-PLA2 levels in human Huh7 hepatoma cells.Both fatty acid and iron metabolism improved after metformin treatment.Metformin alleviated oxidative stress, apoptosis, lipid peroxidation and ferroptosis.Metformin lowered Lp-PLA2 levels in human Huh7 hepatoma cells.Both fatty acid and iron metabolism improved after metformin treatment.Metformin alleviated oxidative stress, apoptosis, lipid peroxidation and ferroptosis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
46. Fe-Co/ZIF-8@SLC-0111-HA 复合纳米平台加强肿瘤化学动力学的可行性.
- Author
-
王振鑫, 周 鹏, 褚福超, 张大振, and 袁 峰
- Abstract
BACKGROUND: The low catalytic activity and lack of targeting of commonly used metal ions have severely limited the clinical application of chemodynamic therapy in tumor treatment. On the other hand, although the composite nanoplatforms are endowed with tumor-targeting functions by surface functionalization, the lack of tumor microenvironment acidity also severely weakens the efficacy of chemodynamic therapy. OBJECTIVE: To prepare novel composite nanoplatforms and assess their feasibility to enhance the effects of chemodynamic therapy at the cellular level. METHODS: SLC-0111-loaded zeolite imidazole framework-8 doped with divalent iron ions (Fe2+) and divalent cobalt ions (Co2+) (Fe-Co/ZIF-8@SLC-0111) was synthesized by ion-exchange reaction and self-assembly, and loaded with hyaluronic acid (HA) by electrostatic adsorption, followed by obtaining the target nanoparticles Fe-Co/ZIF-8@SLC-0111-HA (abbreviated as FC-S). Meanwhile, nanoparticles Fe-Co/ZIF-8-HA (abbreviated as FC) without SLC-0111 were synthesized by the same method. The nanocomposite platform was tested for particle size, zeta potential, surface morphology, in vitro reactive oxygen species generation, and ability to consume glutathione. Human osteosarcoma cell MG-63 and mouse fibroblast cell L929 were used as experimental subjects. The cytotoxicity of FC-S was detected by CCK-8 assay. Human osteosarcoma cell MG-63 was used as the experimental object to detect the cell internalization of FC-S. In addition to H2O2, the effects of FC-S and FC on intracellular pH, carbonic anhydrase 9 protein expression, cell viability and apoptosis, intracellular reactive oxygen species and glutathione content, and mitochondrial membrane potential were investigated. RESULTS AND CONCLUSION: (1) The FC-S composite nanoplatform was successfully prepared with a well-defined rhombic dodecahedral structure, uniform size and good dispersion. Its particle size was about 323 nm; zeta potential was about -11.1 mV, and the nanoplatform had a certain reactive oxygen species generation capacity in vitro. (2) FC-S nanoplatforms accumulated intracellularly in a time-dependent manner and could successfully escape from lysosomes. When the mass concentration of FC-S was ≤ 20 µg/mL, there was no obvious cytotoxicity to MG-63 cells and L929 cells, and 20 µg/mL FC-S was selected to act on MG-63 cells in subsequent experiments. (3) Compared with FC group, the protein expression of carbonic anhydrase 9 in MG-63 cells in FC-S group was decreased (P < 0.01); the intracellular acidic environment was enhanced; the content of reactive oxygen species was increased (P < 0.001); the mitochondrial damage was aggravated; the number of dead cells was increased, and the apoptosis rate was increased (P < 0.001). (4) The results indicate that FC-S, as a novel composite nanoplatform, can effectively improve the weakly acidic microenvironment in tumor cells and enhance the level of intracellular reactive oxygen species production, thus enhancing the efficacy of chemodynamic therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
47. Comparison of the efficacy of alginate nanoparticles containing Cymbopogon citratus essential oil and citral on melanoma and breast cancer cell lines under normoxic and hypoxic conditions.
- Author
-
Karami, Farnaz, Osanloo, Mahmoud, Alipanah, Hiva, Zarenezhad, Elham, Moghimi, Fatemeh, and Ghanbariasad, Ali
- Subjects
THERAPEUTIC use of antineoplastic agents ,THERAPEUTIC use of essential oils ,ALGINATES ,IN vitro studies ,FLOW cytometry ,MELANOMA ,RESEARCH funding ,DATA analysis ,BREAST tumors ,TERPENES ,ESSENTIAL oils ,APOPTOSIS ,ELECTRON microscopy ,DESCRIPTIVE statistics ,REVERSE transcriptase polymerase chain reaction ,CELL lines ,PLANT extracts ,GAS chromatography ,GENE expression ,DRUG efficacy ,MASS spectrometry ,ONE-way analysis of variance ,STATISTICS ,COMPARATIVE studies ,DATA analysis software ,NANOPARTICLES ,HYPOXEMIA ,EVALUATION - Abstract
Background: Solid tumors often develop hypoxic regions, leading to aggressive behavior and increased drug resistance. Methods: The chemical composition of Cymbopogon citratus essential oil (EO) was analyzed using GC-MS. Alginate nanoparticles containing the EO and its primary component, citral, were synthesized via the ionic gelation method. Encapsulation was confirmed using ATR-FTIR analysis. The anticancer efficacy of C. citratus EO, citral, and their respective alginate nanoparticles was evaluated under normoxic (21% oxygen) and hypoxic (1% oxygen) conditions on breast cancer (MDA-MB-231) and melanoma (A-375) cell lines. Additionally, qPCR and flow cytometry were used to assess apoptosis gene expression ratios (Bax/Bcl-2) and levels of apoptosis. Results: Citral (80.98%) was identified as the major component of the EO. Alginate nanoparticles containing C. citratus EO and citral (C. citratus-AlgNPs and citral-AlgNPs) were synthesized with particle sizes of 195 ± 4 nm and 222 ± 9 nm, and zeta potentials of -22 ± 3 mV and − 17 ± 1 mV, respectively. Both samples demonstrated significantly greater efficacy under hypoxic conditions. Citral and C. citratus-AlgNPs had IC
50 values of 27 (19–39) µg/mL and 25 (4-147) µg/mL, respectively, against MDA-MB-231 and A-375 cells. Flow cytometry showed increased apoptosis under hypoxic conditions, with the highest rates observed for citral-AlgNPs and C. citratus-AlgNPs (84 ± 5 and 92 ± 5% in MDA-MB-231 and A-375 cells, respectively). Conclusion: This study demonstrates that alginate nanoparticles enhance the anticancer activity of C. citratus-AlgNPs and citral, particularly under hypoxic conditions, highlighting their potential for hypoxia-targeted cancer therapies. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
48. Reverse hierarchical DED assembly in the cFLIP-procaspase-8 and cFLIP-procaspase-8-FADD complexes.
- Author
-
Yang, Chao-Yu, Tseng, Yi-Chun, Tu, Yi-Fan, Kuo, Bai-Jiun, Hsu, Li-Chung, Lien, Chia-I, Lin, You-Sheng, Wang, Yin-Ting, Lu, Yen-Chen, Su, Tsung-Wei, Lo, Yu-Chih, and Lin, Su-Chang
- Subjects
DEATH receptors ,CASPASES ,CELLULAR signal transduction ,MUTAGENESIS ,APOPTOSIS - Abstract
cFLIP, a master anti-apoptotic regulator, targets the FADD-induced DED complexes of procaspase-8 in death receptor and ripoptosome signaling pathways. Several tumor cells maintain relatively high levels of cFLIP in achieving their immortality. However, understanding the three-dimensional regulatory mechanism initiated or mediated by elevated levels of cFLIP has been limited by the absence of the atomic coordinates for cFLIP-induced DED complexes. Here we report the crystal plus cryo-EM structures to uncover an unconventional mechanism where cFLIP and procaspase-8 autonomously form a binary tandem DED complex, independent of FADD. This complex gains the ability to recruit FADD, thereby allosterically modulating cFLIP assembly and partially activating caspase-8 for RIPK1 cleavage. Our structure-guided mutagenesis experiments provide critical insights into these regulatory mechanisms, elucidating the resistance to apoptosis and necroptosis in achieving immortality. Finally, this research offers a unified model for the intricate bidirectional hierarchy-based processes using multiprotein helical assembly to govern cell fate decisions. FADD binds Casp-8 and then cFLIP to form the FADD-Casp8-cFLIP complex. The authors found that the DED complex could assemble in reverse order, where cFLIP oligomerizes to bind Casp-8. The resultant complex could bind FADD, generating the cFLIP-Casp-8-FADD complex by a different mechanism. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
49. Lats-IN-1 protects cardiac function and promotes regeneration after myocardial infarction by targeting the hippo pathway.
- Author
-
Hua Shen, Qing Wang, Bohan Liu, Yihui Wang, Dandan Zhou, Lin Zhang, and Jinqiang Zhuang
- Subjects
HIPPO signaling pathway ,CARDIAC regeneration ,MYOCARDIAL infarction ,HEART diseases ,HEART failure - Abstract
Introduction: Myocardial infarction (MI), a leading cause of heart failure, is characterized by the loss of cardiomyocytes, which severely limits the heart's regenerative capacity. The Hippo pathway, which regulates cell proliferation and apoptosis, presents a therapeutic target for cardiac regeneration. This study explores the efficacy of Lats-IN-1, a LATS1/2 kinase inhibitor targeting the Hippo pathway, as a novel treatment for MI. Methods: Using male C57BL/6 mice subjected to surgically induced MI, we administered Lats-IN-1 and evaluated the effects on cardiac function, infarct size, cardiomyocyte proliferation, and apoptosis through various assays and echocardiographic assessments. Results: Our results demonstrate that Lats-IN-1 significantly improves cardiac function, as evidenced by enhanced ejection fraction and reduced ventricular dimensions. Additionally, Lats-IN-1 decreased infarct size and apoptosis rates while promoting cardiomyocyte proliferation. These findings suggest that Lats-IN-1 promotes cardiac repair and regeneration. Discussion: By modulating the Hippo pathway and reducing apoptosis markers, Lats-IN-1 represents a promising therapeutic strategy for improving outcomes in heart diseases characterized by cardiomyocyte loss. This study highlights the critical role of the Hippo pathway in facilitating cardiac regeneration. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
50. Oleic acid attenuates asthma pathogenesis via Th1/Th2 immune cell modulation, TLR3/4-NF-κB-related inflammation suppression, and intrinsic apoptotic pathway induction.
- Author
-
Soon-Young Lee, Duc Dat Le, Chun-Sik Bae, Jin Woo Park, Mina Lee, Seung-Sik Cho, and Dae-Hun Park
- Subjects
TH2 cells ,OLEIC acid ,ASTHMATICS ,PATHOLOGICAL physiology ,GENE transfection - Abstract
WHO reported that asthma was responsible for 455,000 deaths in 2019 and asthma patients was evaluated 262 million in May 2023. The incidence is expected to increase as the average life expectancy increases, highlighting asthma as a significant health challenge in an aging society. The etiology of asthma is linked to an imbalance of Th1 and Th2 cells, respiratory inflammation, and pulmonary cell proliferation. The purpose of this study is to investigate the anti-asthmatic effect and potential mechanism of oleic acid. The antiinflammatory effect of oleic acid was evaluated in an LPS-induced RAW 264.7 cell model, and immune modulation and the anti-apoptotic effect were measured in an ovalbumin-induced BALB/c mouse model. A variety of analytical procedures, such as MTT, qPCR, ELISA, Western blotting, immunofluorescence, gene transfection, immunohistochemistry, and several staining methods (Diff Quik, H&E, PAS), were used to evaluate the effectiveness and mechanisms of these methods. The results from in vitro experiments showed that oleic acid could reduce the levels of inflammatory cytokines (TNF-a, IL-6, and IL-1b), and molecular docking studies suggested that oleic acid could interact with TLR3 and TLR4 proteins to form ligand-protein complexes, showing good binding affinity. Additionally, oleic acid attenuated the expression of MAPK pathway components (JNK, p38 MAPK) and NF-kB pathway constituents (IkB, NF-kB, COX-2, PGE2). In vivo results indicated that oleic acid reduced the levels of inflammatory cells (WBCs and eosinophils) and IgE activity, reduced the expression of the Th2 cell transcription factor GATA-3, and decreased the levels of Th2/Th17-related cytokines (IL-4, TNF-a, and IL-6). Oleic acid also alleviated OVA-induced pathological changes in the lung, such as epithelial cell proliferation, inflammatory cell infiltration, and mucus hypersecretion. OVA restored apoptosis in lung epithelial cells by modulating the expression of Bcl-2 and Bax. In summary, oleic acid has potential as a novel candidate for asthma treatment through its ability to regulate immune cells, exert anti-inflammatory effects, and promote apoptosis, thereby ameliorating asthma manifestations. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.