Epithelial Cell Apoptosis Research Articles

Pyrroloquinoline Quinone Alleviates Mitochondria Damage in Radiation-Induced Lung Injury in a MOTS-c-Dependent Manner.

Radiation-induced lung injury (RILI) is a prevalent complication of thoracic tumor radiotherapy and accidental radiation exposure. Pyrroloquinoline quinone (PQQ), a novel vitamin B, plays a crucial role in delaying aging, antioxidation, anti-inflammation, and antiapoptosis. This study aims to investigate the protective effect and mechanisms of PQQ against RILI. C57BL/6 mice were exposed to a 20 Gy dose of X-ray radiation on the entire thorax with or without daily oral administration of PQQ for 2 weeks. PQQ effectively mitigated radiation-induced lung tissue damage, inflammation, oxidative stress, and epithelial cell apoptosis. Additionally, PQQ significantly inhibited oxidative stress and mitochondrial damage in MLE-12 cells. Mechanistically, PQQ upregulated the mRNA and protein levels of MOTS-c in irradiated lung tissue and MLE-12 cells. Knockdown of MOTS-c by siRNA substantially attenuated the protective effects of PQQ on oxidative stress, inflammation, and apoptosis. In conclusion, PQQ alleviates RILI by preserving mitochondrial function through a MOTS-c-dependent mechanism, suggesting that PQQ may serve as a promising nutraceutical intervention against RILI.

Hydramethylnon induces mitochondria-mediated apoptosis in BEAS-2B human bronchial epithelial cells

Typically used household chemicals comprise numerous compounds. Determining mixture toxicity, as observed when using household chemicals containing multiple substances, is of considerable importance from a regulatory perspective. Upon examining the toxic effects of household chemical mixtures, we observed that hydramethylnon combined with tetramethrin resulted in synergistic toxicity. To determine the unknown toxicity mechanism of hydramethylnon, which carries the risk of inhalation exposure when using household chemicals, we conducted a further investigation using BEAS-2B cells, a human bronchial epithelial cell line. Hydramethylnon-induced cytotoxicity was determined following 24 and 48 h of exposure using the water-soluble tetrazolium 1 and lactate dehydrogenase assays. To elucidate the toxicity mechanism, we utilized flow cytometry and measured the levels of apoptosis-related proteins and caspase activities. Given that hydramethylnon, as an insecticide, disrupts the mitochondrial electron transfer chain, we analyzed the relevant mechanisms, including mitochondrial superoxide levels as well as the mitochondrial membrane potential (MMP). Hydramethylnon dose-dependently induced BEAS-2B cell apoptosis via the intrinsic pathway. Furthermore, it significantly increased mitochondrial superoxide levels and disrupted the MMP. Pre-treatment with a caspase inhibitor (Z-DEVD-FMK) confirmed that hydramethylnon induced caspase-dependent apoptosis. Apoptosis, a key event in the toxicological process of chemicals, can lead to lung diseases, including fibrosis and cancer. The results of the present study suggest a mechanism of toxicity of hydramethrylnon, an organofluorine biocide whose toxicity has been little studied, to the lung epithelium. Considering the potential risks associated with inhalation exposure, these results highlight the need for careful management and regulation of hydramethylnon.

MTORC1 and mTORC2 Co-Protect against Cadmium-Induced Renal Tubular Epithelial Cell Apoptosis and Acute Kidney Injury by Regulating Protein Kinase B.

The potential threat of cadmium (Cd)-induced acute kidney injury (AKI) is increasing. In this study, our primary goal was to investigate the individual roles played by mTOR complexes, specifically mTORC1 and mTORC2, in Cd-induced apoptosis in mouse kidney cells. We constructed a mouse model with specific deletion of Raptor/Rictor renal cells. Inhibitors and activators of mTORC1 or mTORC2 were also applied. The effects of protein kinase B (AKT) activation and autophagy were studied. Both mTORC1 and mTORC2 were found to mediate the antiapoptotic mechanism of renal cells by regulating the AKT activity. Inhibition of mTORC1 or mTORC2 exacerbated Cd-induced kidney cell apoptosis, suggesting that both proteins exert antiapoptotic effects under Cd exposure. We further found that the AKT activation plays a key role in mTORC1/TORC2-mediated antiapoptosis, protecting Cd-exposed kidney cells from apoptosis. We also found that mTOR activators inhibited excessive autophagy, alleviated apoptosis, and promoted cell survival. These findings provide new insights into the regulatory mechanisms of mTOR in renal diseases and provide a theoretical basis for the development of novel therapeutic strategies to treat renal injury.

Inflammatory Signaling via PEIZO1 Engages and Enhances the LPS-Mediated Apoptosis during Clinical Mastitis.

Bovine clinical mastitis is characterized by inflammation and immune responses, with apoptosis of mammary epithelial cells as a cellular reaction to infection. PIEZO1, identified as a mechanotransduction effector channel in nonruminant animals and sensitive to both mechanical stimuli or inflammatory signals like lipopolysaccharide (LPS). However, its role in inflammatory processes in cattle has not been well-documented. The aim of this study was to elucidate the in situ expression of PIEZO1 in bovine mammary gland and its potential involvement in clinical mastitis. We observed widespread distribution and upregulation of PIEZO1 in mammary epithelial cells in clinical mastitis cows and LPS-induced mouse models, indicating a conserved role across species. In vitro studies using mammary epithelial cells (MAC-T) revealed that LPS upregulates PIEZO1. Notably, the effects of PIEZO1 artificial activator Yoda1 increased apoptosis and NLRP3 expression, effects mitigated by PIEZO1 silencing or NLRP3 inhibition. In conclusion, the activation of the PIEZO1-NLRP3 pathway induces abnormal apoptosis in mammary epithelial cells, potentially serving as a regulatory mechanism to combat inflammatory responses to abnormal stimuli.

High fluoride aggravates cadmium-mediated nephrotoxicity of renal tubular epithelial cells through ROS-PINK1/Parkin pathway

Fluoride (F) and cadmium (Cd) as well known environmental pollutants can cause nephrotoxicity to damage human health, while the joint toxicity of F and Cd to the renal tubular epithelial cells remains still elusive. The interactive influence between F and Cd in oxidative stress, apoptosis, and mitochondrial autophagy of renal tubular epithelial cells was explored. Cells were submitted to varying concentrations with of NaF (1, 5, 10, and 15 μg/mL) combined with CdCl2·2.5H2O (1 μg/mL) for 12 h. Following this, the combined cytotoxicity was assessed. Our results show that different doses of F had varying effects on Cd-mediated nephrotoxicity, with a synergistic effect observed in the high F (15 μg/mL) co-treated with Cd. In response to the Cd induction, the high F treatment resulted in the formation of multiple autophagosomes and notably increased the levels of LDH, ROS, and MMP. It also elevated the MDA contents while decreasing the activities of SOD, GSH-Px, and CAT. Additionally, it yielded a higher Bax/Bcl-2 ratio, which further promotes the apoptotic process. The treatment also disturbed energy metabolism, resulting in a reduction of both ATP and ADP. Furthermore, autophagy-related genes and proteins, including PINK1, Parkin, LC3A, LC3B, and SQSTM1, were significantly improved. In brief, high F of 15 μg/mL aggravated Cd-mediated nephrotoxicity of renal tubular epithelial cells via the ROS-PINK1/Parkin pathway.

MiR-495 promotes intestinal epithelial cell apoptosis through downregulation of Sphingosine-1-phosphate.

Many pathological conditions lead to defects in intestinal epithelial integrity and loss of barrier function; Sphingosine-1-phosphate (S1P) has been shown to augment intestinal barrier integrity, though the exact mechanisms are not completely understood. We have previously shown that overexpression of Sphingosine Kinase 1 (SphK1), the rate limiting enzyme for S1P synthesis, significantly increased S1P production and cell proliferation. Here we show that microRNA 495 (miR-495) upregulation led to decreased levels of SphK1 resultant from a direct effect at the SphK1 mRNA. Increasing expression of miR-495 in intestinal epithelial cells resulted in decreased proliferation and increased susceptibility to apoptosis. Transgenic expression of miR-495 inhibited mucosal growth, as well as decreased proliferation in the crypts. The intestinal villi also expressed decreased levels of barrier proteins and exaggerated damage upon exposure to cecal ligation-puncture. These results implicate miR-495 as a critical negative regulator of intestinal epithelial protection and proliferation through direct regulation of SphK1, the rate limiting enzyme critical for production of S1P.

Conversation between host and gut microbiota unveils a “silver bullet” therapeutic option for chemotherapy

Chemotherapy is associated with the induction of intestinal microbiota dysbiosis and gastrointestinal injuries. In this Cell Host & Microbe issue, Anderson etal. demonstrate that chemotherapy-induced epithelial cell apoptosis drives microbiota imbalance and transcriptional rewiring, which in turn delays intestinal recovery.

Apoptosis and Oxidative Stress in Human Intestinal Epithelial Caco-2 Cells Caused by Marine Phycotoxin Azaspiracid-2.

When humans consume seafood contaminated by lipophilic polyether phycotoxins, such as azaspiracids (AZAs), the toxins are mainly leached and absorbed in the small intestine, potentially causing intestinal damage. In this study, human intestinal epithelial Caco-2 cells were used to investigate the adverse effects of azaspiracid-2 (AZA-2) on human intestinal epithelial cells. Cell viability, apoptosis, oxidative damage and mitochondrial ultrastructure were investigated, and ribonucleic acid sequence (RNA-seq) analysis was applied to explore the potential mechanisms of AZA-2 toxicity to Caco-2 cells. Results showed that AZA-2 significantly reduced the proliferation of Caco-2 cells in a concentration-dependent response, and the 48 h EC50 of AZA-2 was 12.65 nmol L-1. AZA-2 can induce apoptosis in Caco-2 cells in a dose-dependent manner. Visible mitochondrial swelling, cristae disintegration, membrane rupture and autophagy were observed in Caco-2 cells exposed to AZA-2. Reactive oxygen species (ROS) and malondialdehyde (MDA) content were significantly increased in Caco-2 cells after 48 h of exposure to 1 and 10 nmol L-1 of AZA-2. Transcriptome analysis showed that KEGG pathways related to cellular oxidative damage and lipid metabolism were affected, mainly including mitophagy, oxidative phosphorylation, cholesterol metabolism, vitamin digestion and absorption, bile secretion and the peroxisome proliferator-activated receptor signaling pathway. The cytotoxic effects of AZA-2 on Caco-2 cells may be associated with ROS-mediated autophagy and apoptosis in mitochondrial cells. Results of this study improve understanding of the cytotoxicity and molecular mechanisms of AZA-2 on Caco-2 cells, which is significant for protecting human health.

Ssc-miR-101-3p inhibits hypoxia-induced apoptosis and inflammatory response in alveolar type-II epithelial cells of Tibetan pigs via targeting FOXO3

Tibetan pigs are a unique swine strain adapted to the hypoxic environment of the plateau regions in China. The unique mechanisms underlying the adaption by Tibetan pigs, however, are still elusive. Only few studies have investigated hypoxia-associated molecular regulation in the lung tissues of animals living in the plateau region of China. Our previous study reported that ssc-miR-101-3p expression significantly differed in the lung tissues of Tibetan pigs at different altitudes, suggesting that ssc-miR-101-3p plays an important role in the adaptation of Tibetan pigs to high altitude. To understand the underlying molecular mechanism, in this study, the target genes of ssc-miR-101-3p and their functions were analyzed via various methods including qRT-PCR and GO and KEGG pathway enrichment analyses. The action of ssc-miR-101-3p was investigated by culturing alveolar type-II epithelial cells (ATII) of Tibetan pigs under hypoxic conditions and transfecting ATII cells with vectors overexpressing or inhibiting ssc-miR-101-3p. Overexpression of ssc-miR-101-3p significantly increased the proliferation of ATII cells and decreased the expression of inflammatory and apoptotic factors. The target genes of ssc-miR-101-3p were significantly enriched in FOXO and PI3K-AKT signaling pathways required to mitigate lung injury. Further, FOXO3 was identified as a direct target of ssc-miR-101-3p. Interestingly, ssc-miR-101-3p overexpression reversed the damaging effect of FOXO3 in the ATII cells. In conclusion, ssc-miR-101-3p targeting FOXO3 could inhibit hypoxia-induced apoptosis and inflammatory response in ATII cells of Tibetan pigs. These results provided new insights into the molecular mechanisms elucidating the response of lung tissues of Tibetan pigs to hypoxic stress.

Histone deacetylase inhibitor, Trichostatin A mitigates ionizing radiation induced redox imbalance by regulating NRF2/GPX4/PINK1/PARKIN signaling in mice intestine.

Gastrointestinal-acute radiation syndrome (GI-ARS) caused by moderate to high doses of ionizing radiation exposurecontribute to early death in humans. GI injury is also a common adverse effect seen in cancer patients undergoing abdominal/pelvic radiotherapy. Currently, no countermeasure agents have been approved for medical management of GI-ARS. The present study aims to evaluate the mechanism of action of Trichostatin A(TSA), a pan histone deacetylaseinhibitor, against radiation-induced GI injury. TSA (150ng/kg bw) was administered to mice 1h and 24h after 15Gy abdominal irradiation. Expression of various markers of oxidative stress, mitochondrial dysfunction, and apoptosis were checked in the jejunum, and their possible regulation throughthe Nrf2 signaling pathway was evaluated. TSA administered post-irradiation (15Gy + TSA) elevated intestinal total antioxidant and glutathione levels by regulating the expression of Slc7A11 and antioxidant proteins, GCLC, GPX4, and TXNRD1. Improved mitochondrial membrane potential, ATP levels, downregulation of mitochondrial quality control proteins, (PINK1 and PARKIN), and differential regulation of the apoptotic proteins, (BAX, PUMA and BCL2) with reduced intestinal epithelial cell apoptosis in the TSA-adminstered groupwere observed. TSA also upregulated Nrf2 in the presence of its specific inhibitor, ML385, suggesting its involvement in regulating Nrf2 signaling during oxidative stress induced by radiation in intestine. H & E stained jejunumcross-sections revealed that TSA mitigated radiation-mediated intestinalinjury in mice. Present findingsindicate that TSA is beneficial in mitigating the damaging effects of ionizing radiation in the intestine.

Inhibition of mitochondrial over-division by (+)-14,15-Dehydrovincamine attenuates cisplatin-induced acute kidney injury via the JNK/Mff pathway

Cisplatin-induced acute kidney injury (AKI) is characterized by mitochondrial damage and apoptosis, and safe and effective therapeutic agents are urgently needed. Renal tubular epithelial cells, the main site of AKI, are enriched with a large number of mitochondria, which are crucial for the progression of AKI with an impaired energy supply. Vincamine has anti-inflammatory and antioxidant effects in mouse AKI models. As a natural compound derived from Tabernaemontana pandacaqui, (+)-14, 15-Dehydrovincamine and Vincamine differ in structure by only one double bond, and the role and exact mechanism of (+)-14, 15-Dehydrovincamine remains to be elucidated in AKI. The present study demonstrated that (+)-14,15-Dehydrovincamine significantly ameliorated mitochondrial dysfunction and maintained mitochondrial homeostasis in a cisplatin-induced AKI model. Furthermore, (+)-14,15-Dehydrovincamine ameliorates cytochrome C-dependent apoptosis in renal tubular epithelial cells. c-Jun NH2-terminal kinase (JNK) was identified as a potential target protein of (+)-14,15-Dehydrovincamine attenuating AKI by network pharmacological analysis. (+)-14,15-Dehydrovincamine inhibited cisplatin-induced JNK activation, mitochondrial fission factor (Mff) phosphorylation, and dynamin-related protein 1 (Drp1) translocation to the mitochondria in renal tubular epithelial cells. Meanwhile, the JNK activator anisomycin restored Mff phosphorylation and Drp1 translocation, counteracting the protective effect of (+)-14,15-Dehydrovincamine on mitochondrial dysfunction in cisplatin-induced TECs injury. In conclusion, (+)-14,15-Dehydrovincamine reduced mitochondrial fission, maintained mitochondrial homeostasis, and attenuated apoptosis by inhibiting the JNK/Mff/Drp1 pathway, which in turn ameliorated cisplatin-induced AKI.

Metabolite-based inter-kingdom communication controls intestinal tissue recovery following chemotherapeutic injury

Cytotoxic chemotherapies have devastating side effects, particularly within the gastrointestinal tract. Gastrointestinal toxicity includes the death and damage of the epithelium and an imbalance in the intestinal microbiota, otherwise known as dysbiosis. Whether dysbiosis is a direct contributor to tissue toxicity is a key area of focus. Here, from both mammalian and bacterial perspectives, we uncover an intestinal epithelial cell death-Enterobacteriaceae signaling axis that fuels dysbiosis. Specifically, our data demonstrate that chemotherapy-induced epithelial cell apoptosis and the purine-containing metabolites released from dying cells drive the inter-kingdom transcriptional re-wiring of the Enterobacteriaceae, including fundamental shifts in bacterial respiration and promotion of purine utilization-dependent expansion, which in turn delays the recovery of the intestinal tract. Inhibition of epithelial cell death or restriction of the Enterobacteriaceae to homeostatic levels reverses dysbiosis and improves intestinal recovery. These findings suggest that supportive therapies that maintain homeostatic levels of Enterobacteriaceae may be useful in resolving intestinal disease.

Palmitic acid-induced cell death: impact of endoplasmic reticulum and oxidative stress, mitigated by L-citrulline.

Palmitic acid (PA), the most abundant saturated free fatty acids, induces apoptosis in bovine mammary epithelial cells. It is suggested that oxidative stress and endoplasmic reticulum (ER) stress are key mechanisms underlying PA-induced cell death. This study aimed to investigate the interaction between ER stress and oxidative stress during PA-induced cell death in MAC-T cells. Additionally, we examined whether L-citrulline can protect against PA-induced damage of MAC-T cells. MAC-T cells were treated with 4-phenyl butyric acid (4-PBA) or N-acetyl-L-cysteine (NAC) to inhibit PA-induced ER stress and oxidative stress, respectively. MAC-T cells were pretreated with or without L-citrulline for 48 h followed by PA treatment. Cell viability was measured with MTT assays. Intracellular reactive oxygen species (ROS) levels in MAC-T cells were assessed using 5-(and-6)-chloromethyl- 2`,7`-dichlorodihydrofluorescein diacetate acetyl ester dye. Real-time qPCR was used to explore the regulation of genes associated with oxidative stress, and ER stress genes. Western blotting analysis was also carried out. 4-PBA significantly reduced PA-induced mRNA expressions of activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), nuclear factor (erythroid-derived 2)-like 2 (NRF2), and intracellular ROS levels. Furthermore, NAC dramatically reduced PA-induced ROS levels and the mRNA expressions of NRF2, ATF4, and CHOP. L-citrulline pretreatment effectively rescued cell viability decreased by PA. Moreover, L-citrulline pretreatment significantly downregulated the PA-induced upregulation of GRP78, ATF4, and CHOP mRNA expression, and protein expression of p-PERK and cleaved caspase-3. PA increased intracellular ROS levels and NRF2 mRNA expression, whereas L-citrulline pretreatment remarkably reduced these levels. Both ER and oxidative stresses interact during PA-induced cell death in MAC-T cells, and L-citrulline could attenuate this cell death by inhibiting ER and oxidative stresses. Therefore, L-citrulline may be a promising supplement for protecting against PA-induced cell death in bovine MECs during the lactation period of dairy cows.

ALKBH5-Mediated m6A Modification Drives Apoptosis in Renal Tubular Epithelial Cells by Negatively Regulating MUC1.

Dysregulation of renal tubular epithelial cell (RTEC) apoptosis is one of the critical steps underlying the occurrence and development of nephrolithiasis. Although N6-methyladenosine (m6A) modification has been extensively studied and associated with various pathologic processes, research onits specific role in RTEC injury and apoptosis remains limited. In this study, we found that overexpression of ALKBH5 reduced the level of m6A modification in RTEC cells and notably promoted RTEC apoptosis. Further mechanism studies revealed that ALKBH5 mainly decreased the m6A level on the mRNA of Mucin 1 (MUC1) gene in RTECs. Moreover, ALKBH5 impaired the stability of MUC1mRNA in RTECs, leading to attenuated expression of MUC1. Finally, we determined that the ALKBH5-MUC1 axis primarily facilitated RTEC apoptosis by regulating the PI3K/Akt signaling pathway. This study revealed the critical role of the ALKBH5-MUC1-PI3K/Akt regulatory system in RTEC apoptosis and provided new therapeutic targets for treating nephrolithiasis.

Swertiamarin ameliorates 2, 4, 6-trinitrobenzenesulfonic acid-induced colitis in mice by inhibiting intestinal epithelial cell apoptosis

To investigate the mechanism by which swertiamarin (STM) ameliorates CD-like colitis in mice. A Caco-2 cell model of TNF-α-stimulated apoptosis was established and divided into three groups: Con, TNF-α and STM, and the effects of STM on apoptosis and barrier function were assessed by Tunel staining, western blotting, immunofluorescence, and transepithelial electric resistance (TEER). A mouse model of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) -induced CD-like colitis was established to assess the effects of STM on colitis, intestinal barrier function and epithelial cell apoptosis. The regulatory role of the PI3K/AKT pathway in STM-induced resistance to intestinal epithelial cell apoptosis was investigated in both the cell model and mouse models. TUNEL staining showed that in Caco-2 cells with TNF-α stimulation, STM treatment significantly reduced the percentage of TUNEL-stained cells (P<0.05). STM obviously reduced TNF-α-induced enhancement of cleaved-caspase 3 and Bax expressions (P<0.05), increased Bcl-2 expression (P<0.05), protected intestinal barrier integrity and function by restoring transepithelial electrical resistance (TEER) of the cells, promoted normal localization and expressions of the tight junction proteins (ZO1 and claudin 1) (P<0.05), and inhibited the expression of pro-inflammatory factors (IL-6 and CCL3) (P<0.05) in TNF-α-stimulated Caco-2 cells. In the mouse models, STM significantly alleviated TNBS-induced CD-like colitis and intestinal barrier dysfunction (P<0.05) as shown by improved weight loss, lowered Disease Activity Index (DAI) score and inflammation score, reduction of IL-6 and CCL3 release, and restoration of intestinal barrier permeability, colonic TEER, bacterial translocation, and localization and expressions of the tight junction proteins. Mechanistically, STM inhibited the expressions of p-PI3K and p-AKT in both the cell model and mouse model(P<0.05), and treatment with 740Y-P (a PI3K/AKT pathway activator) significantly attenuated the inhibitory effect of STM on TNF-α-induced apoptosis in Caco-2 cells (P<0.05). STM inhibits intestinal epithelial cell apoptosis at least in part by suppressing activation of the PI3K/AKT pathway to ameliorate intestinal barrier dysfunction and colitis in mice.

Indole‑3‑propionic acid alleviates intestinal epithelial cell injury via regulation of the TLR4/NF‑κB pathway to improve intestinal barrier function.

Indole‑3‑propionic acid (IPA), a product of Clostridium sporogenes metabolism, has been shown to improve intestinal barrier function. In the present study, in vitro experiments using NCM460 human colonic epithelial cells were performed to investigate how IPA alleviates lipopolysaccharide (LPS)‑induced intestinal epithelial cell injury, with the aim of improving intestinal barrier function. In addition, the underlying mechanism was explored. NCM460 cell viability and apoptosis were measured using the Cell Counting Kit‑8 assay and flow cytometry, respectively. The integrity of the intestinal epithelial barrier was evaluated by measuring transepithelial electrical resistance (TEER). The underlying molecular mechanism was explored using western blotting, immunofluorescence staining, a dual luciferase reporter gene assay and quantitative PCR. The results showed that 10 µg/ml LPS induced the most prominent decrease in cell viability after 24 h of treatment. By contrast, IPA effectively inhibited LPS‑induced apoptosis in the intestinal epithelial cells. Additionally, >0.5 mM IPA improved intestinal barrier function by increasing TEER and upregulating the expression of tight junction proteins (zonula occludens‑1, claudin‑1 and occludin). Furthermore, IPA inhibited the release of pro‑inflammatory cytokines (IL‑1β, IL‑6 and TNF‑α) in a dose‑dependent manner and this was achieved via regulation of the Toll‑like receptor 4 (TLR4)/myeloid differentiation factor 88/NF‑κB and TLR4/TRIF/NF‑κB pathways. In conclusion, IPA may alleviate LPS‑induced inflammatory injury in human colonic epithelial cells. Taken together, these results suggest that IPA may be a potential therapeutic approach for the management of diseases characterized by LPS‑induced intestinal epithelial cell injury and intestinal barrier dysfunction.

Electrochemiluminescence assay for the impact of Ganoderma lucidum polysaccharides on resisting arsenic-induced apoptosis

Ganoderma lucidum (G. lucidum) is a traditional edible fungus with strong medicinal value. G. lucidum polysaccharides (GLP) encapsulate many of the key beneficial properties of this species, providing a valuable tool for the treatment of a range of diseases. The present study was developed to explore the protective benefits of GLP treatment in the context of arsenic poisoning. Through microscopy and flow cytometry experiments, NaAsO2 was found to induce rat tracheal epithelial (RTE) cell apoptosis, together with reductions in cell surface epidermal growth factor receptor (EGFR) expression. GLP treatment, however, was able to reduce apoptosis rates and elevate the expression of EGFR relative to NaAsO2-treated cells. GLP extracts (50, 100, 200 mg·mL−1) prepared from four types of G. lucidum were administered to RTE cells damaged with arsenic, revealing limited differences in position resistance among these varieties. This work provides reference for the pharmaceutical and medical research of G. lucidum.

Pathogenesis, Diagnosis, and Treatment of Infectious Rhinosinusitis.

Rhinosinusitis is a common inflammatory disease of the sinonasal mucosa and paranasal sinuses. The pathogenesis of rhinosinusitis involves a variety of factors, including genetics, nasal microbiota status, infection, and environmental influences. Pathogenic microorganisms, including viruses, bacteria, and fungi, have been proven to target the cilia and/or epithelial cells of ciliated airways, which results in the impairment of mucociliary clearance, leading to epithelial cell apoptosis and the loss of epithelial barrier integrity and immune dysregulation, thereby facilitating infection. However, the mechanisms employed by pathogenic microorganisms in rhinosinusitis remain unclear. Therefore, this review describes the types of common pathogenic microorganisms that cause rhinosinusitis, including human rhinovirus, respiratory syncytial virus, Staphylococcus aureus, Pseudomonas aeruginosa, Aspergillus species, etc. The damage of mucosal cilium clearance and epithelial barrier caused by surface proteins or secreted virulence factors are summarized in detail. In addition, the specific inflammatory response, mainly Type 1 immune responses (Th1) and Type 2 immune responses (Th2), induced by the entry of pathogens into the body is discussed. The conventional treatment of infectious sinusitis and emerging treatment methods including nanotechnology are also discussed in order to improve the current understanding of the types of microorganisms that cause rhinosinusitis and to help effectively select surgical and/or therapeutic interventions for precise and personalized treatment.

Effect of acacetin on inhibition of apoptosis in Helicobacter pylori-infected gastric epithelial cell line.

Helicobacter pylori (H. pylori) infection can cause extensive apoptosis of gastric epithelial cells, serving as a critical catalyst in the progression from chronic gastritis, gastrointestinal metaplasia, and atypical gastric hyperplasia to gastric carcinoma. Prompt eradication of H. pylori is paramount for ameliorating the pathophysiological conditions associated with chronic inflammation of the gastric mucosa and the primary prevention of gastric cancer. Acacetin, which has multifaceted pharmacological activities such as anti-cancer, anti-inflammatory, and antioxidative properties, has been extensively investigated across various domains. Nevertheless, the impact and underlying mechanisms of action of acacetin on H. pylori-infected gastric mucosal epithelial cells remain unclear. To explore the defensive effects of acacetin on apoptosis in H. pylori-infected GES-1 cells and to investigate the underlying mechanisms. GES-1 cells were treated with H. pylori and acacetin in vitro. Cell viability was assessed using the CCK-8 assay, cell mortality rate via lactate dehydrogenase assay, alterations in cell migration and healing capacities through the wound healing assay, rates of apoptosis via flow cytometry and TUNEL staining, and expression levels of apoptosis-associated proteins through western blot analysis. H. pylori infection led to decreased GES-1 cell viability, increased cell mortality, suppressed cell migration, increased rate of apoptosis, increased expressions of Bax and cle-caspase3, and decreased Bcl-2 expression. Conversely, acacetin treatment enhanced cell viability, mitigated apoptosis induced by H. pylori infection, and modulated the expression of apoptosis-regulatory proteins by upregulating Bcl-2 and downregulating Bax and cleaved caspase-3. Acacetin significantly improved GES-1 cell viability and inhibited apoptosis in H. pylori-infected GES-1 cells, thereby exerting a protective effect on gastric mucosal epithelial cells.

SiTGF-β1 and pirfenidone contained Ionizable-Liposomal nanodrug for enhanced treatment of Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a challenging interstitial lung disease characterized by heterogeneous manifestations and significant mortality. Due to the relative complexity of IPF pathogenesis, currently approved clinical drugs mainly for anti-inflammatory or anti-fibrotic present limited disease containment and insufficient damage repair, falling far short of previous expectations. To address this limitation, we developed an ionizable liposome nanodrug (named as TPNPs) co-loaded with small interfering RNA targeting TGF-β1 (siTGF-β1) and pirfenidone (PFD) for enhanced IPF therapy. The siTGF-β1 (blocking TGF-β signaling pathway) and PFD were carefully selected and integrated in consideration of their crucial roles in endothelial mesenchymal transition, alveolar epithelial cell apoptosis, and fibroblast differentiation and migration, which are closely related to IPF development. As a result, TPNPs exhibited synergistic enhancement effects against the damage of alveolar epithelial cells and fibroblasts in vitro. Notably, repeated administration of TPNPs mitigated the injury to alveolar epithelium, inhibited the excessive accumulation of extracellular matrix (ECM), and alleviated the destruction of lung, thereby synergistically ameliorating the lung function in a bleomycin (BLM)-induced murine model. This work provides a promising therapeutic strategy that combines nucleic acid with small molecule for enhanced treatment of IPF.