Evaluation of the Correlation Between Nasal Secretion ECP-MPO Test Papers and Immune Markers in Subcutaneous Immunotherapy of Dust Mites.

Purpose: Up to now, there is no generally accepted biomarker to indicate the clinical response of immunotherapy. This study mainly analyzed the correlation between eosinophil cationic protein-myeloperoxidase (ECP-MPO) test papers and other immunotherapy indices in subcutaneous immunotherapy of dust mites and to explore whether the test paper can be used as an auxiliary index to quickly evaluate the efficacy of immunotherapy. Patients and methods: This study included 53 participants who received subcutaneous immunotherapy at the allergy clinic of Renmin Hospital of Wuhan University and 28 control participants. Six visits were conducted during a prospective study over one year. The results of the ECP-MPO test paper, nasal secretion eosinophil smear and count, nasal secretion ECP concentration, and clinical symptom scores were collected during five follow-up visits after the start of subcutaneous immunotherapy. Th1/Th2/Th17 cytokines, chemokines, IgE, IgG4 against dust mite components, and ECP concentrations were detected in the serum of participants at baseline, six months, and one year after subcutaneous immunotherapy. Results: The ECP test paper is not only easy to operate, but also can effectively and quickly detect the concentrations of ECP in the nasal secretion and diagnose allergic rhinitis. Symptom score is an important index for evaluating clinical immune efficacy, during subcutaneous immunotherapy, the ECP test paper showed a positive correlation with the symptom score. Simultaneously, during immunotherapy, the changes in the chromogenic grading of the test paper were synchronized with the changes in inflammatory cytokines and eosinophilic chemokines in Th2 cells of serum dust mite IgE. The sIgG4 against dust mites weakly negatively correlated with the concentration of ECP in nasal secretions and the color classification of the ECP test paper. Conclusion: The ECP-MPO test paper has a certain correlation with subcutaneous immunotherapy markers of allergic rhinitis, indicating that the ECP test paper may become an auxiliary biomarker to replace other complex laboratory tests.

Organizing pneumonia secondary to pulmonary tuberculosis: A case report.

BACKGROUND: Organizing pneumonia secondary to pulmonary tuberculosis is rare. Moreover, the temporal boundary between pulmonary tuberculosis and secondary organizing pneumonia has not been defined. We report a case of secondary organizing pneumonia associated with pulmonary tuberculosis occurring after nine months of antituberculosis treatment. CASE SUMMARY: A 54 years old man, previously diagnosed with pulmonary tuberculosis and tuberculous pleurisy, underwent nine months of antituberculosis treatment. Follow-up lung computed tomography revealed multiple new subpleural ground-glass opacities in both lungs, and a lung biopsy confirmed organizing pneumonia. Treatment continued with anti-tuberculosis agents and hormone therapy, and subsequent dynamic pulmonary computed tomography exams demonstrated improvement in lesion absorption. No disease recurrence was observed after corticosteroid therapy discontinuation. CONCLUSION: When treating patients with active pulmonary tuberculosis, if an increase in lesions is observed during anti-tuberculosis treatment, it is necessary to consider the possibility of tuberculosis-related secondary organizing pneumonia, timely lung biopsy is essential for early intervention.

Safety and feasibility of enhanced recovery after surgery-based management model for ambulatory pediatric surgical procedures.

BACKGROUND: There is still some room for optimizing ambulatory pediatric surgical procedures, and the preoperative and postoperative management quality for pediatric patients needs to be improved. AIM: To discuss the safety and feasibility of the enhanced recovery after surgery (ERAS)-based management model for ambulatory pediatric surgical procedures. METHODS: We selected 320 pediatric patients undergoing ambulatory surgery from June 2023 to January 2024 at The First People's Hospital of Liangshan Yi Autonomous Prefecture. Of these, 220 received ERAS-based management (research group) and 100 received routine management (control group). General information, postoperative ambulation activities, surgical outcomes (operation time, postoperative gastrointestinal ventilation time, and hospital stay), postoperative pain visual analogue scale, postoperative complications (incision infection, abdominal distension, fever, nausea, and vomiting), and family satisfaction were compared. RESULTS: The general information of the research group (sex, age, disease type, single parent, family history, etc.) was comparable to that of the control group (P > 0.05), but the rate of postoperative (2 h, 4 h, and 6 h after surgery) ambulation activities was statistically higher (P < 0.01), and operation time, postoperative gastrointestinal ventilation time, and hospital stay were markedly shorter (P < 0.05). The research group had lower visual analogue scale scores (P < 0.01) at 12 h and 24 h after surgery and a lower incidence of total postoperative complications than the control group (P = 0.001). The research group had higher family satisfaction than the control group (P = 0.007). CONCLUSION: The ERAS-based management model was safe and feasible in ambulatory pediatric surgical procedures and worthy of clinical promotion.

The involvement of the Stat1/Nrf2 pathway in exacerbating Crizotinib-induced liver injury: implications for ferroptosis.

Crizotinib carries an FDA hepatotoxicity warning, yet analysis of the FAERS database suggests that the severity of its hepatotoxicity risks, including progression to hepatitis and liver failure, might be underreported. However, the underlying mechanism remains poorly understood, and effective intervention strategies are lacking. Here, mRNA-sequencing analysis, along with KEGG and GO analyses, revealed that DEGs linked to Crizotinib-induced hepatotoxicity predominantly associate with the ferroptosis pathway which was identified as the principal mechanism behind Crizotinib-induced hepatocyte death. Furthermore, we found that ferroptosis inhibitors, namely Ferrostatin-1 and Deferoxamine mesylate, significantly reduced Crizotinib-induced hepatotoxicity and ferroptosis in both in vivo and in vitro settings. We have also discovered that overexpression of AAV8-mediated Nrf2 could mitigate Crizotinib-induced hepatotoxicity and ferroptosis in vivo by restoring the imbalance in glutathione metabolism, iron homeostasis, and lipid peroxidation. Additionally, both Stat1 deficiency and the Stat1 inhibitor NSC118218 were found to reduce Crizotinib-induced ferroptosis. Mechanistically, Crizotinib induces the phosphorylation of Stat1 at Ser727 but not Tyr701, promoting the transcriptional inhibition of Nrf2 expression after its entry into the nucleus to promote ferroptosis. Meanwhile, we found that MgIG and GA protected against hepatotoxicity to counteract ferroptosis without affecting or compromising the anti-cancer activity of Crizotinib, with a mechanism potentially related to the Stat1/Nrf2 pathway. Overall, our findings identify that the phosphorylation activation of Stat1 Ser727, rather than Tyr701, promotes ferroptosis through transcriptional inhibition of Nrf2, and highlight MgIG and GA as potential therapeutic approaches to enhance the safety of Crizotinib-based cancer therapy.

Locally unlocks prodrugs by radiopharmaceutical in tumor for cancer therapy.

Chemotherapy is the first-line treatment for cancer, but its systemic toxicity can be severe. Tumor-selective prodrug activation offers promising opportunities to reduce systemic toxicity. Here, we present a strategy for activating prodrugs using radiopharmaceuticals. This strategy enables the targeted release of chemotherapeutic agents due to the high tumor-targeting capability of radiopharmaceuticals. [18F]FDG (2-[18F]-fluoro-2-deoxy-D-glucose), one of the most widely used radiopharmaceuticals in clinics, can trigger Pt(IV) complex for controlled release of axial ligands in tumors, it might be mediated by hydrated electrons generated by water radiolysis resulting from the decay of radionuclide 18F. Its application offers the controlled release of fluorogenic probes and prodrugs in living cells and tumor-bearing mice. Of note, an OxaliPt(IV) linker is designed to construct an [18F]FDG-activated antibody-drug conjugate (Pt-ADC). Sequential injection of Pt-ADC and [18F]FDG efficiently releases the toxin in the tumor and remarkably suppresses the tumor growth. Radiotherapy is booming as a perturbing tool for prodrug activation, and we find that [18F]FDG is capable of deprotecting various radiotherapy-removable protecting groups (RPGs). Our results suggest that tumor-selective radiopharmaceutical may function as a trigger, for developing innovative prodrug activation strategies with enhanced tumor selectivity.

Genome-wide association studies reveal the genetic basis of growth and carcass traits in Sichuan Shelduck.

China has abundant local duck resource populations, and evaluating the characteristics of these breeds will help improve development and utilization. In this study, we conducted the first investigations of growth and slaughter performance on Sichuan Shelduck (n = 240), an endangered duck local breed. The average body weight is 1497.91 g at 90 d of age. According to the growth curve through data recorded every 2 wk, we observed a low relative growth rate (RGR) for the early growth stage. The RGR shows a decreasing trend with age increasing in the stage from 0 to 56 d of age. The SNP-based heritability estimation showed the growth rate has a relatively high heritability, indicating high genetic stability for this trait. In the correlation analysis, the percentage of leg muscle is positively correlated with the absolute growth rate (AGR) at 28 to 42 d of age, whereas it is negatively correlated with the earlier stages, exhibiting a time-specific correlation result. Additionally, genome-wide association studies (GWAS) identified PCSK6, TOX2, and TOMM7 as potential candidate genes influencing AGR (42-56) and AGR (56-90), while the candidate genes of slaughter traits were PTP4A2, FAM110B, TOX, UBXN2B, and FCHSD2. These results provide an important reference for further understanding the genetic basis of growth and meat production performance of Sichuan Shelduck.

A novel strategy with in vivo characterization, extraction, isolation and activity evaluation for discovery of absorbed anti-inflammatory oligosaccharides from Zhu-Ling decoction.

Zhu-Ling decoction (ZLD), a classical traditional Chinese medicine (TCM) formula, is used for the treatment of chronic kidney diseases. However, the structure and activity of absorbed oligosaccharides (OSs) in ZLD are not clear. In this study, a novel strategy with in vivo characterization, extraction, isolation, activity evaluation was established and applied to identify absorbed anti-inflammatory OSs in ZLD. The results revealed that 30 OSs (22 reducing and 8 non-reducing OSs) and 11 OSs (7 reducing and 4 non-reducing OS) were characterized from ZLD in vitro and in vivo by using UPLC/Q-TOF-MS with PMP derivatization, respectively. Among them, a series of -1 â†’ 3-ß-D-Glcp-OSs were isolated and identified by HPLC-HILIC-UVD-ELSD, SPHPLC-HILIC-RID, monosaccharide composition, MS and 1D/2D-NMR spectroscopy, including laminaritriose, laminaritetraose, laminaripentaose, laminarihexaose, laminariheptaose, laminarioctaose and laminarinonaose. Moreover, the 4 non-reducing absorbed OSs were identified by comparison with reference standards, including sucrose, trehalose, raffinose and stachyose. Among them, laminaritriose, laminaritetraose and laminaripentaose significantly inhibited TNF-α and IL-6 levels in LPS-induced HK-2 cell and exerted significant anti-inflammatory effects via the NF-κB and Akt/mTOR signaling pathways. Together, our work provides a novel strategy for discovery of absorbed anti-inflammatory OSs and broadens new horizons for the discovery of in vivo pharmacodynamic substances in TCM formulas.

Exercise Prescription in Individuals with Prehypertension and Hypertension: Systematic Review and Meta-Analysis.

Background: The prevalence of prehypertension and hypertension has been increasing over the years, and is closely related to cardiovascular and cerebrovascular diseases. Exercise is an effective method of lifestyle intervention, and it aims to lower blood pressure and control other risks. Studies have shown that different modes of exercise have varying effects on blood pressure, and individuals with prehypertension or hypertension need to carry out this intervention by using personalized modes of exercise. Methods: We conducted a systematic review and meta-analysis to evaluate the effects of different modes of exercise regimens on systolic blood pressure, diastolic blood pressure and heart rate in individuals with high-normal blood pressure and hypertension. We included 27 trials, and 2731 individuals were under 8 exercise regimens. Stata12.0 statistical software was used for statistical analysis. Results: Heat pools significantly reduced systolic blood pressure (SBP) by 15.62 mmHg (95% confidence interval [CI]: -23.83, -7.41), and cycling reduced SBP by 14.76 mmHg (-17.04, -12.48). Two to three types of aerobic exercise performed at the same time also significantly reduced diastolic blood pressure (DBP) by 5.61 mmHg (-7.71, -3.52), and isometric handgrip training exercise reduced DBP by 5.57 mmHg (-7.48, -3.66). Cycling also significantly reduced heart rate (HR) by 9.57 beats/minute (-11.25, -7.90). Conclusions: The existing literature suggests that different types of exercise can effectively reduce the levels of SBP, DBP and HR in individuals with prehypertension or hypertension.

Identification of candidate genes associated with primary feathers of tianfu nonghua ducks based on Genome-wide association studies.

The primary feathers of ducks have important economic value in the poultry industry. This study quantified the primary feather phenotype of Nonghua ducks, including the primary feathers' length, area, distribution of black spots, and feather symmetry. And genome-wide association analysis was used to screen candidate genes that affect the primary feather traits. The genome-wide association study (GWAS) results identified the genetic region related to feather length (FL) on chromosome 2. Through Linkage disequilibrium (LD) analysis, candidate regions (chr2: 115,246,393-116,501,448 bp) were identified and were further annotated to 5 genes: MRS2, GPLD1, ALDH5A1, KIAA0319, and ATP9B. Secondly, candidate regions related to feather black spots were identified on chromosome 21. Through LD analysis, the candidate regions (chr21: 163,552-2,183,853 bp) were screened and further annotated to 47 genes. Among them, STK4, CCN5, and YWHAB genes were related to melanin-related pathways or pigment deposition, which may be key genes affecting the distribution of black spots on feathers. In addition, we also screened 125 genes on multiple chromosomes that may be related to feather symmetry. Among them, significant SNPs on chromosome 1 were further identified as candidate regions (chr1: 142,118,209-142,223,605 bp) through LD analysis and annotated into 2 genes, TGFBRAP1 and LOC113839965. These results reported the genetic basis of the primary feather from multiple phenotypes, and offered valuable insights into the genetic basis for the growth and development of duck feathers and feather color pattern.

Three-dimensional printing the navigation template for precise percutaneous renal puncture to treat pyonephrosis on a porcine model and a patient ：a case report.

Objective: Percutaneous nephrolithotomy (PCNL) is the main method for pyonephrosis or lithotripsy in urology. However, it often comes with high risk, as the inaccurate puncture inevitably causes bleeding, intra- and post-operative complications. So, a new inter-disciplinary approach is needed to perform the puncture more accurately. Methods: 3 signs made of lead were marked onto the skin of the posterior side of the waist of a domestic pig or a patient, which was scanned by computed tomography (CT). Based on the CT images, the computer design and the 3D printing, a navigation template made of the transparent resin material is constructed. They were attached onto the surgical area on pig or patient according to the signs. During the PCNL, with this template, the puncture position, angle and depth were optimized in order to precisely enter the targeted renal pelvis or calices. Results: With the 3D navigation templates, 18G puncture needles were used to enter the renal pelvis upon performing the PCNL on a porcine model and a patient. On the porcine model, the urine outflow was observed with minimal complication. Post-operative CT scans revealed that the needle was located in the renal pelvis. For the patient case, the puncture point was designed to target the calix with stone. No obvious bleeding and complication was found in renal puncture with template. Conclusions: The navigation template was made with the combination of 3D printing, CT images and computer design. This template allows for accurate puncture of the renal pelvis or calix. Surgical improvement in kidney stones and pyonephrosis was observed in porcine model and patient case. In the future, prospective, trandomized, controlled clinical trials are needed to further confirm its advantage.

HMGA2 promotes resistance against paclitaxel by targeting the p53 signaling pathway in colorectal cancer cells.

Colorectal cancer is one of the most common malignancies and ranks second in terms of cancer-related mortality worldwide due to its metastasis, drug resistance, and reoccurrence. High-mobility gene group A2 (HMGA2) is overexpressed in colorectal cancer, contributing to the aggressiveness of tumor malignance, and promotes drug resistance in many types of cancer. However, the underlying molecular mechanism of HMGA2 is yet to be elucidated. In this study, we showed that HMGA2 is overexpressed in colorectal cancer tissue, and knockdown of HMGA2 significantly inhibited colorectal cancer cell growth and migratory capability. HMGA2 regulates the cancer cell response to a widely used anti-cancer drug, paclitaxel (PTX). HMGA2 knockdown increased cell death, whereas HMGA2 overexpression decreased cell death after PTX treatment. Furthermore, lower reactive oxygen species (ROS) levels and mitochondrial potential were detected in HMGA2 overexpression cells after PTX treatment. However, HMGA2 knockdown produced the opposite effect. RNA sequencing showed a p53 signaling pathway-dependent regulation in HMGA2 knockdown cells. Combined with p53 inhibitors and HMGA2 knockdown, a synergetic effect of more cell death was observed in colorectal cancer cells after PTX treatment. Thus, we showed that HMGA2 can activate p53 signaling to regulate colorectal cancer cell death after PTX treatment. Altogether, our results reveal novel insights into the molecular mechanisms underlying HMGA2-mediated cancer cell resistance against PTX and highlight the potential of targeting HMGA2 and p53 signaling for the therapeutic investigation of colorectal cancer.

Follicular CD8+ T cells promote immunoglobulin production and demyelination in multiple sclerosis and a murine model.

Emerging evidence underscores the importance of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8+ T cells (CD8+CXCR5+ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8+CXCR5+ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8+CXCR5+ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8+CXCR5+ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8+CXCR5+ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG35-55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses.

Palladium-Catalyzed Enantioselective Multicomponent Cross-Coupling of Trisubstituted Olefins.

The development of a catalytic method for stereogenic carbon center formation holds immense significance in organic synthesis. Transition-metal-catalyzed cross-coupling reaction has been regarded as a straightforward and efficient tool for stereoselectively forging C-C bond. Nevertheless, the creation of acyclic all-carbon quaternary-containing vicinal stereocenters remains notoriously challenging within the domain of cross-coupling chemistry despite their prominence in various bioactive small molecules. Herein, we describe a palladium-catalyzed asymmetric multicomponent cross-coupling of trisubstituted alkene with aryl diazonium salts and arylboronic acids to realize the formation of tertiary-quaternary carbon centers with high regio-, distereo-, and enantioselectivity. Specifically, the precise manipulation of the stereoconfiguration of trisubstituted alkenes enables the divergent stereoselective cross-coupling reaction, thus allowing for the facile construction of all four enantiomers. Harnessing the ligand-swap strategy involving a chiral bisoxazoline and an achiral fumarate individually accelerates the enantioselective migratory insertion and reductive elimination step in the cross-coupling process, as supported by density functional theory (DFT) calculations, thus obviating the requirement for a neighboring directing group within the internal olefin skeleton.

Efficacy of angiotensin receptor blockers for nocturnal blood pressure reduction: a systematic review and meta-analysis.

BACKGROUND: Nocturnal blood pressure (BP) is correlated with an increased risk of cardiovascular events and is an important predictor of cardiovascular death in hypertensive patients. OBJECTIVE: Nocturnal BP control is of great importance for cardiovascular risk reduction. This systematic review and meta-analysis aimed to explore the efficacy of angiotensin receptor blockers (ARBs) for nocturnal BP reduction in patients with mild to moderate hypertension. METHODS: PICOS design structure was used to formulate the data extraction. All statistical calculations and analyses were performed with R. RESULTS: Seventy-seven studies with 13,314 participants were included. The overall analysis indicated that nocturnal BP drop varied considerably among different ARBs. Allisartan (13.04 [95% CI (-18.41, -7.68)] mmHg), olmesartan (11.67 [95% CI (-14.12, -9.21)] mmHg), telmisartan (11.11 [95% CI (-12.12, -10.11)] mmHg) were associated with greater reduction in nocturnal systolic BP. In the aspect of the nocturnal-diurnal BP drop ratio, only allisartan was greater than 1. While, the variation tendency of last 4-6 h ambulatory BP was basically consistent with nocturnal BP. Additionally, allisartan showed improvement effect in the proportion of patients with dipping BP pattern. CONCLUSIONS: This study demonstrates that for patients with mild to moderate hypertension, allisartan, olmesartan and telmisartan have more advantages in nocturnal BP reduction among the ARBs, while allisartan can reduce nighttime BP more than daytime BP and improve the dipping pattern.

This meta-analysis explores the efficacy of Angiotensin II AT1 receptor antagonists (ARBs) on nocturnal blood pressure (BP) reduction in mild to moderate hypertension.The results demonstrate that for patients with mild to moderate hypertension, allisartan, olmesartan and telmisartan have more advantages in nocturnal BP reduction among the ARBs.Allisartan can reduce nighttime BP more effectively than daytime BP, which also improve the dipping pattern.

Advances in bacteria-based drug delivery systems for anti-tumor therapy.

In recent years, bacteria have gained considerable attention as a promising drug carrier that is critical in improving the effectiveness and reducing the side effects of anti-tumor drugs. Drug carriers can be utilised in various forms, including magnetotactic bacteria, bacterial biohybrids, minicells, bacterial ghosts and bacterial spores. Additionally, functionalised and engineered bacteria obtained through gene engineering and surface modification could provide enhanced capabilities for drug delivery. This review summarises the current studies on bacteria-based drug delivery systems for anti-tumor therapy and discusses the prospects and challenges of bacteria as drug carriers. Furthermore, our findings aim to provide new directions and guidance for the research on bacteria-based drug systems.

Covalent targeted radioligands potentiate radionuclide therapy.

Targeted radionuclide therapy, in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation, has addressed unmet clinical needs and improved outcomes for patients with cancer1-4. A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue, which remains a major challenge5,6. A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution. Here we installed a sulfur (VI) fluoride exchange (SuFEx) chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance. When the engineered radiopharmaceutical binds to the tumour-specific protein, the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the 'click' SuFEx reaction. The application of this strategy to a fibroblast activation protein (FAP) inhibitor (FAPI) triggered more than 80% covalent binding to the protein and almost no dissociation for six days. In mice, SuFEx-engineered FAPI showed 257% greater tumour uptake than did the original FAPI, and increased tumour retention by 13-fold. The uptake in healthy tissues was rapidly cleared. In a pilot imaging study, this strategy identified more tumour lesions in patients with cancer than did other methods. SuFEx-engineered FAPI also successfully achieved targeted ß- and α-radionuclide therapy, causing nearly complete tumour regression in mice. Another SuFEx-engineered radioligand that targets prostate-specific membrane antigen (PSMA) also showed enhanced therapeutic efficacy. Considering the broad scope of proteins that can potentially be ligated to SuFEx warheads, it might be possible to adapt this strategy to other cancer targets.

Unlocking the power of Zc3h12c: Orchestrating Macrophage activation and elevating the innate immune response.

The activation of macrophages, essential for the innate defense against invading pathogens, revolves around Toll-like receptors (TLRs). Nevertheless, a comprehensive understanding of the molecular mechanisms governing TLR signaling in the course of macrophage activation remains to be fully clarified. Although Zc3h12c was originally identified as being enriched in organs associated with macrophages, its precise function remains elusive. In this study, we observed a significant induction of Zc3h12c in macrophages following stimulation with TLR agonists and pathogens. Overexpression of Zc3h12c significantly mitigated the release of TNF-α and IL-6 triggered by lipopolysaccharide (LPS), whereas depletion of Zc3h12c increased the production of the cytokines mentioned above. Notably, the expression of IFN-ß was not influenced by Zc3h12c. Luciferase reporter assays revealed that Zc3h12c could suppress the TNF-α promoter activity. Moreover, Zc3h12c exerted a notable inhibitory effect on JNK, ERK, p38, and NF-κB signaling induced by LPS. In summary, the findings of our study suggest that Zc3h12c functions as a robust suppressor of innate immunity, potentially playing a role in the pathogenesis of infectious diseases.

Naringenin relieves paclitaxel-induced pain by suppressing calcitonin gene-related peptide signalling and enhances the anti-tumour action of paclitaxel.

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) commonly causes neuropathic pain, but its pathogenesis remains unclear, and effective therapies are lacking. Naringenin, a natural dihydroflavonoid compound, has anti-inflammatory, anti-nociceptive and anti-tumour activities. However, the effects of naringenin on chemotherapy-induced pain and chemotherapy effectiveness remain unexplored. EXPERIMENTAL APPROACH: Female and male mouse models of chemotherapy-induced pain were established using paclitaxel. Effects of naringenin were assessed on pain induced by paclitaxel or calcitonin gene-related peptide (CGRP) and on CGRP expression in dorsal root ganglia (DRG) and spinal cord tissue. Additionally, we examined peripheral macrophage infiltration, glial activation, c-fos expression, DRG neuron excitability, microglial M1/M2 polarization, and phosphorylation of spinal NF-κB. Furthermore, we investigated the synergic effect and related mechanisms of naringenin and paclitaxel on cell survival of cancer cells in vitro. KEY RESULTS: Systemic administration of naringenin attenuated paclitaxel-induced pain in both sexes. Naringenin reduced paclitaxel-enhanced CGRP expression in DRGs and the spinal cord, and alleviated CGRP-induced pain in naïve mice of both sexes. Naringenin mitigated macrophage infiltration and reversed paclitaxel-elevated c-fos expression and DRG neuron excitability. Naringenin decreased spinal glial activation and NF-κB phosphorylation in both sexes but influenced microglial M1/M2 polarization only in females. Co-administration of naringenin with paclitaxel enhanced paclitaxel's anti-tumour effect, impeded by an apoptosis inhibitor. CONCLUSION AND IMPLICATIONS: Naringenin's anti-nociceptive mechanism involves CGRP signalling and neuroimmunoregulation. Furthermore, naringenin facilitates paclitaxel's anti-tumour action, possibly involving apoptosis. This study demonstrates naringenin's potential as a supplementary treatment in cancer therapy by mitigating side effects and potentiating efficacy of chemotherapy.

Role of oxidative stress-induced ferroptosis in cancer therapy.

Ferroptosis is a distinct mode of cell death, distinguishing itself from typical apoptosis by its reliance on the accumulation of iron ions and lipid peroxides. Cells manifest an imbalance between oxidative stress and antioxidant equilibrium during certain pathological contexts, such as tumours, resulting in oxidative stress. Notably, recent investigations propose that heightened intracellular reactive oxygen species (ROS) due to oxidative stress can heighten cellular susceptibility to ferroptosis inducers or expedite the onset of ferroptosis. Consequently, comprehending role of ROS in the initiation of ferroptosis has significance in elucidating disorders related to oxidative stress. Moreover, an exhaustive exploration into the mechanism and control of ferroptosis might offer novel targets for addressing specific tumour types. Within this context, our review delves into recent fundamental pathways and the molecular foundation of ferroptosis. Four classical ferroptotic molecular pathways are well characterized, namely, glutathione peroxidase 4-centred molecular pathway, nuclear factor erythroid 2-related factor 2 molecular pathway, mitochondrial molecular pathway, and mTOR-dependent autophagy pathway. Furthermore, we seek to elucidate the regulatory contributions enacted by ROS. Additionally, we provide an overview of targeted medications targeting four molecular pathways implicated in ferroptosis and their potential clinical applications. Here, we review the role of ROS and oxidative stress in ferroptosis, and we discuss opportunities to use ferroptosis as a new strategy for cancer therapy and point out the current challenges persisting within the domain of ROS-regulated anticancer drug research and development.

Role of pyroptosis-related cytokines in the prediction of lung cancer.

Objectives: Lung cancer is the leading cause to induce cancer-related mortality. Effective biomarkers for prediction the occurrence of lung cancer is urgently needed. Our previous studies indicated that pyroptosis-related cytokines TNF-α, IFN-γ, MIP-1α, MIP-1ß, MIP-2 and IP-10 is important to influence the efficacy of chemotherapy drug in lung cancer tissues. But the role of pyroptosis-related cytokines in prediction the occurrence of lung cancer is still unknown. Methods: Blood samples were collected from 258 lung cancer patients at different stage and 80 healthy volunteers. Serum levels of pyroptosis-related cytokines including TNF-α, IFN-γ, MIP-1α, MIP-1ß, MIP-2 and IP-10 were measured by Cytometric Bead Array (CBA). ROC curve was performed to evaluate the cut-off value and diagnosis value for prediction and diagnosis of lung cancer. Results: Compared with control group, the levels of IP-10, MIP-1α, MIP-1ß, MIP-2 and TNF-α were significantly higher in lung cancer patients (45.5 (37.1-56.7): 57.2 (43.0-76.5), 34.4 (21.8-75.2): 115.4 (96.6-191.2), 49.3 (25.6-78.7): 160.5 (124.9-218.6), 22.6 (17.8-31.2): 77.9 (50.1-186.5), 3.80 (2.3-6.2): 10.3 (5.7-16.6)), but the level of IFN-γ was decreased in the patients (12.38 (9.1-27.8): 5.9 (3.5-9.7)). All the above cytokines were significantly associated with the diagnosis of lung cancer, and the AUC values of IFN-γ, IP-10, MIP-1α, MIP-1ß, MIP-2, and TNF-α were 0.800, 0.656, 0.905, 0.921, 0.914, and 0.824. And the AUC can rise to 0.986 after combining the above factors, and the sensitivity and specificity also up to 96.7 % and 93.7 %, respectively. Additionally, TNF-α (r = 0.400, P < 0.01), MIP-2 (r = 0.343, P < 0.01), MIP-1α (r = 0.551, P < 0.01) and MIP-1ß (r = 0.403, p < 0.01) were positively associated with occurrence of lung cancer, but IFN-γ (r = -0.483, p < 0.01) was negatively associated with occurrence of lung cancer. As far as the potential of early diagnosis of lung cancer, TNF-α (AUC = 0.577), MIP-1α (AUC = 0.804) and MIP-1ß (AUC = 0.791) can predict the early stage of lung cancer, and combination of the above three cytokines has a better predictive efficiency (AUC = 0.854). Conclusion: Our study establishes a link between the levels of IP-10, MIP-1α, MIP-1ß, MIP-2, TNF-α and IFN-γ and diagnosis of lung cancer. Besides, we observed a synergistic effect of these five pyroptosis-related cytokines in diagnosing lung cancer patient, suggesting their potential as biomarkers for lung cancer diagnosis. Moreover, the combination of TNF-α, MIP-1α and MIP-1ß are also potential predictors for the early diagnosis of lung cancer.