Ferroptosis is a recently identified form of regulated cell death, characterized by iron-dependent accumulation of intracellular reactive oxygen species. It plays a significant role in the onset and progression of various immune-mediated diseases and has become a focal point in contemporary biomedical research. Vascular calcification (VC) is associated with a range of cardiovascular diseases, including myocardial infarction stroke, aortic and peripheral artery disease, heart failure, chronic kidney disease, diabetes mellitus, and aortic valve stenosis, posing significant threats to public health. However, therapeutic options remain limited, highlighting the urgent need for further investigation. In recent years, several pioneering studies have indicated that ferroptosis activation significantly contributes to the progression of VC. These findings have attracted growing attention from researchers across related disciplines. Nevertheless, the underlying mechanisms are not yet fully understood, indicating the necessity for further exploration. This study focuses on a special review of the molecular regulatory pathways of ferroptosis and VC, systematically summarizes the confirmed core pathways, explores the potential regulatory directions, and discusses the clinical transformation value combined with the mechanism, so as to provide exclusive and practical theoretical reference and research ideas for the in-depth research in this field and the targeted therapy of VC.

ObjectivesThis study aims to explore the role and investigate mechanisms of β-Cryptoxanthin (BCX) in high glucose (HG)-induced podocyte injury and renal dysfunction.MethodsIn this study, db/db mice were orally treated with BCX. Blood glucose, body weight, urinary albumin creatinine ratio (ACR) were recorded to evaluate the mice renal function. The H&E, PAS staining, and transmission electron microscopy (TEM) were utilized to examine the effect of BCX on the morphological changes of glomeruli in db/db mice. In addition, reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP) level, ATP level, and SA-β-gal staining were used to assess the podocyte oxidative damage, mitochondrial dysfunction and senescence. Furthermore, the effects of BCX on Nrf2/HO-1 signaling pathway were evaluated in vivo and in vitro through Western blotting, immunohistochemistry and immunofluorescence analysis.ResultsIn vivo, BCX reversed glomerular mesangial matrix expansion and reduced proteinuria in db/db mice, as well as decreased glomerular oxidative stress and kidney aging. Similarly, in vitro study showed that BCX effectively alleviated the oxidative stress, mitochondrial dysfunction, and senescence induced by HG in podocytes. Furthermore, we identified that the antioxidative effects of BCX are associated with the activation of Nrf2/HO-1 signaling pathway, and that Nrf2 knockdown partially abrogated the protective effects of BCX in vitro.ConclusionOur study demonstrated for the first time that BCX alleviates podocyte injury in DKD by promoting Nrf2/HO-1 signaling pathways. BCX may be a potential candidate compound for preventing Diabetic kidney disease (DKD).

INTRODUCTION:Cerebral swelling and brain injury in ischemic stroke are closely related to increased vasopressin (VP) secretion. How to alleviate ischemic brain injury by suppressing VP hypersecretion through simply available approaches remains to be established. METHODS:Using a rat model of middle cerebral artery occlusion (MCAO), testing effects of the intranasal application of low concentration saline-0.09% NaCl (IAL) on brain damage, VP neuronal activity, synaptic inputs, astrocytic plasticity, and olfactory bulb (OB) activity in immunohistochemistry, patch-clamp recording, Western blotting, and co-immunoprecipitation. RESULTS:IAL reduced MCAO-evoked neurological disorders, brain swelling, injury and loss of neurons, increase in c-Fos expression, and excitation of supraoptic VP neurons. The effects of IAL on VP neurons were associated with its suppression of MCAO-evoked increase in the frequency of excitatory synaptic inputs and decrease in the expression of glial fibrillary acidic protein (GFAP) filaments around VP neurons. MCAO and IAL also caused similar but weaker reactions in putative oxytocin neurons. In the OB, MCAO increased the firing rate of mitral cells on the MCAO side, which was reduced by IAL. A direct hypotonic challenge of OB slices increased the expression of glutamine synthetase and GFAP filaments in the glomerular bodies while reducing the firing rate of mitral cells. Blocking aquaporin 4 activity in the supraoptic and paraventricular nuclei on the MCAO side reduced MCAO-evoked VP increase and brain damage. CONCLUSION:IAL reduces ischemic stroke-evoked brain injury in association with suppression of VP neuronal activity through reducing excitatory synaptic inputs and astrocytic process retraction, which likely result from reducing mitral cell activation in ischemic side.

Objective This study aimed to examine the mechanism of hyperphosphatemia-induced vascular calcification (HPVC). Methods Primary human aortic smooth muscle cells and rat aortic rings were cultured in Dulbecco’s modified Eagle’s medium supplemented with 0.9 mM or 2.5 mM phosphorus concentrations. Type III sodium-dependent phosphate cotransporter-1 (Pit-1) small interfering RNA and phosphonoformic acid (PFA), a Pit-1 inhibitor, were used to investigate the effects and mechanisms of Pit-1 on HPVC. Calcium content shown by Alizarin red staining, expression levels of Pit-1, and characteristic molecules for phenotypic transition of vascular smooth muscle cells were examined. Results Hyperphosphatemia induced the upregulation of Pit-1 expression, facilitated phenotypic transition of vascular smooth muscle cells, and led to HPVC in cellular and organ models. Treatment with Pit-1 small interfering RNA or PFA significantly inhibited Pit-1 expression, suppressed phenotypic transition, and attenuated HPVC. Conclusions Our findings suggest that Pit-1 plays a pivotal role in the development of HPVC. The use of PFA as a Pit-1 inhibitor has the potential for therapeutic intervention in patients with HPVC. However, further rigorous clinical investigations are required to ensure the safety and efficacy of PFA before it can be considered for widespread implementation in clinical practice.

Vascular calcification (VC) has a high incidence in patients with chronic kidney disease, which is a worldwide public health problem and presents a heavy burden to society. Hypoxia-inducible factor (HIF)-1α, the active subunit of HIF-1, has been reported to play a vital role in high phosphate-induced VC. However, the underlying mechanism is still undetermined, and effective treatment is unavailable. In the present study, human aortic smooth muscle cells (HASMCs) were cultured under normal or high phosphate media conditions. HIF-1α small interfering RNA and overexpression plasmids were employed to regulate HIF-1α expression. Phosphonoformic acid was employed to restrain the function of type III sodium-dependent phosphate cotransporter 1 (Pit-1). The expression levels of HIF-1α, Pit-1, runt-related transcription factor 2 (Runx2), and smooth muscle 22 alpha (SM22α) were evaluated, and the calcium contents were also examined. Cell growth was assessed using an MTT assay. High phosphate stimulation caused an upregulation in HIF-1α and Pit-1 expression levels and induced calcium depositions in HASMCs. Upregulation of Runx2 expression accompanied by downregulation of SM22α expression was observed in the high phosphate group. Following the suppression of HIF-1α expression, there was a concomitant attenuation in Pit-1 expression, calcium deposition, the alteration of phenotypic transition marker genes, and vice versa. The most serious calcium deposition was noted in HASMCs cultured under high phosphate conditions which were pretreated with a HIF-1α overexpression plasmid. However, when the biological functions of Pit-1 were restrained, the putative serious calcium deposition was not formed even in HASMCs transfected with a HIF-1α overexpression plasmid. The findings confirmed that HIF-1α regulated Pit-1 expression and exerted its pro-calcifying effect through Pit-1, which identified HIF-1α and Pit-1 as therapeutic targets for high phosphate-induced VC.

The efficacy of sphenopalatine ganglion (SPG) block for pain control after endoscopic sinus surgery remains controversial. We conduct a systematic review and meta-analysis to explore the influence of SPG block on pain intensity after endoscopic sinus surgery. We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through June 2019 for randomized controlled trials (RCTs) assessing the efficacy of SPG block for pain management after endoscopic sinus surgery. This meta-analysis is performed using the random-effect model. Six RCTs are included in the meta-analysis. Overall, compared with control group for endoscopic sinus surgery, SPG block is associated with the decrease in pain scores at 6 h (Std. MD =  − 0.71; 95% CI =  − 1.08 to − 0.34; P = 0.0002) and 24 h (Std. MD =  − 0.51; 95% CI =  − 0.87 to − 0.14; P = 0.006), the number of rescue analgesics (RR = 0.26; 95% CI = 0.16 to 0.42; P < 0.00001) and incidence of nausea and vomiting (RR = 0.52; 95% CI = 0.30–0.89; P = 0.02), but demonstrate no obvious impact on pain scores at 2 h (Std. MD =  − 0.99; 95% CI =  − 2.80–0.83; P = 0.29) or headache (RR = 1.30; 95% CI = 0.38–4.46; P = 0.67). SPG block can provide additional benefits for pain management after endoscopic sinus surgery.

The high incidence of vascular calcification (VC) in patients with chronic kidney disease (CKD) has become an important clinical subject. Hyperphosphatemia is a primary cause of CKD-related VC. Intravenous iron sucrose (IS) is commonly used to treat anemia in CKD patients, and is effective and well tolerated worldwide. However, the interaction between iron and VC remains controversial, and the underlying mechanisms are yet to be clarified. In the present study, ex vivo normal rat aortic rings were cultured with various concentrations of phosphate and IS, and the levels of calcium and iron depositions, oxidative injury, as well as phenotypic marker genes were detected. To the best of our knowledge, the present study is the first to report that IS is a double-edged sword in high phosphate media-induced VC which not only alleviates VC in a dose-dependent manner but also leads to iron overload in vasculature when in high concentration. IS is a promising agent for VC prevention in patients with hyperphosphatemia and iron deficiency. Meanwhile, the appropriate blood concentration of IS in patients with hyperphosphatemia needs to be explored clinically.

Chemotherapeutic drugs resistance such as cisplatin (DDP) is one of the important factors for poor prognosis of ovarian cancer. LncRNA UCA1 plays a regulatory role in tumor and inflammation. Whether LncRNA UCA1 involves in ovarian cancer cisplatin resistance is unclear. SKOV3 cell and cisplatin-resistant strain cell SKOV3/DDP were cultured and LncRNA UCA1 expression was analyzed by Real time PCR. LncRNA UCA1 plasmid and LncRNA UCA1 siRNA were transfected into SKOV3/DDP, followed by analysis of cell proliferation by MTT assay, Caspase 3 activity, cell invasion, Bax and Bc1-2 expression by Real time PCR as well as ERK/P38 signaling protein by Western blot. LncRNA UCA1 was significantly upregulated in SKOV3/DDP compared to SKOV3 cell (P < 0.05). LncRNA UCA1 siRNA significantly down-regulated LncRNA UCA1 expression in SKOV3/DDP, inhibit cell proliferation, promote Caspase 3 activity, inhibit cell invasion, increase Bax expression, decrease Bcl-2 and ERK/P38 expression (P < 0.05). LncRNA UCA1 plasmid upregulated LncRNA UCA1 and significantly reversed the above changes in comparison to control group (P < 0.05). LncRNA UCA1 is increased in SKOV3/DDP cells. Targeting LncRNA UCA1 inhibits apoptosis of ovarian cancer cisplatin-resistant cells via reducing ERK/P38 signaling activity, inhibit cell proliferation and invasion.

Vascular calcification (VC) is highly prevalent in chronic kidney disease (CKD), especially in patients with end stage renal disease and is strongly associated with cardiovascular morbidity and mortality. Clinical observations have demonstrated that hyperphosphatemia and hyperglycemia can accelerate VC. Spironolactone (SPL) has been proven to improve cardiovascular outcomes in clinical trials and its protective effect on VC has been reported recently; however, the underlying mechanisms are not completely understood and require further investigation. Furthermore, the current CKD rat models that are used to research VC do not match well with the clinical characteristics of CKD patients. Aortic rings were obtained from male Sprague-Dawley rats, then cultured in different media with varying phosphorus and glucose concentrations to investigate the effects and the possible mechanisms, as well as the effective serum concentrations of SPL, on VC and type III sodium-dependent phosphate cotransporter-1 (Pit-1) expression. SPL dose-dependently alleviated VC by suppressing the phenotypic transition of vascular smooth muscle cell (VSMCs) through downregulation of Pit-1 in a high phosphorus medium and even in a high phosphorus combined with high glucose medium. The combined effects of hyperglycemia and hyperphosphatemia on the calcification of aortic rings ex vivo were demonstrated. In conclusion to the best of our knowledge, this article is the first report on the effective serum concentrations of SPL capable of protecting VSMCs from calcification and provides the first experimental evidence for the combined effects of hyperglycemia and hyperphosphatemia on VC of aortic rings. Additionally, the Pit-1 protein level may be a novel index for evaluating the magnitude of VC in CKD patients.

Vascular calcification (VC) is common in patients with diabetes and/or chronic kidney disease (CKD). It is strongly associated with cardiovascular morbidity and mortality. Hyperphosphatemia caused by CKD induces the transformation of vascular smooth muscle cells (VSMCs) into chondrocytes or osteoblast-like cells. Hyperglycemia may also accelerate VC. However, the exact mechanisms of this remain unclear. The effects of simultaneous hyperphosphatemia and hyperglycemia require investigation. CKD rat models are typically used to study VC, which are far removed from the clinical situations of patients with CKD. The present study cultured human aortic smooth muscle cells (HASMCs) in normal, hyperphosphatemic and/or hyperglycemic conditions for 14 days. Alizarin red staining, calcification content, VSMC differentiation marker gene expression, phenotypic osteoblast gene expression and type III sodium-dependent phosphate cotransporter-1 (Pit-1) protein expression was examined. Hyperphosphatemia and hyperglycemia had combined effects in promoting calcification, phenotypic transition and Pit-1 expression in cultured HASMCs. In the present study, the combined effects of hyperphosphatemia and hyperglycemia on the calcification and phenotypic transition of HASMCs were demonstrated. Hyperphosphatemia combined with hyperglycemia medium should be considered an appropriate experimental model to study VC in diabetic kidney disease (DKD). Pit-1 should be considered as a promising index of VC.

Objective: To determine the effect of postoperative hepatic arterial infusion chemotherapy (HAIC) on long-term survival of patients with pancreatic cancer (PC) after radical pancreatectomy. Methods: A total of 87 patients with PC underwent radical pancreatectomy in the First People's Hospital affiliated to Huzhou Normal College between June 2008 and May 2013. Among these patients, after surgery, 43 received two sessions of HAIC followed by four sessions of systemic chemotherapy (HAIC group), while 44 received six sessions of systemic chemotherapy alone (control group). Both the HAIC and systemic chemotherapy regimen included 5-fluorouracil (1,000 mg/m(2)) as a 5-h infusion on day 1, and gemcitabine (800 mg/m(2)) as an over 30-min infusion on days 1 and 8. The toxicity, complication, and long-term survival were retrospectively compared. Results: No significant difference in patient characteristics between the two groups was found. No chemotherapy-related deaths were recorded, and no significant difference in toxicities was observed between the two groups. The 5-year disease-free survival probability did not differ between the two groups (P=0.2029, hazard ratio for recurrence=0.7561; 95% CI=0.4768-1.1989, by the log-rank test). The HAIC group had significantly higher 5-year overall survival probability (P=0.0288, hazard ratio for death=0.6059; 95% CI=0.3734-0.9832, by the log-rank test) and higher 5-year hepatic metastases-free survival probability (P=0.0321, hazard ratio for hepatic metastases=0.5006; 95% CI=0.2546-0.9843, by the log-rank test) than the control group. Conclusions: Postoperative HAIC has the potential to prevent hepatic metastases and increase long-term survival probability of patients with PC after radical pancreatectomy.

Macrophage-derived foam cells are well known for their key role in development of atherosclerosis (AS). The present study aimed to examine whether dioscin exerts anti-atherosclerotic activity and inhibits foam cell formation. A high-fat induced AS model and ox-LDL treated macrophages were established and received treatment of dioscin. Anti-atherosclerotic activity in vivo was assessed by atherosclerotic lesions size and aortic lipid contents. Macrophage formed foam cells were positively identified by oil red o staining. Moreover, the expression of LOX-1 and NF-κB in aorta tissue and macrophages was examined by western blotting assay. Our results showed that dioscin not only reduced the levels of plasma lipid, TNF-a, IL-1β and IL-6, but also inhibited atherosclerotic development in AS rats, as evidenced by decreased atherosclerotic lesions size and aortic lipid level. In vitro study revealed dioscin directly reduced foam cell formation, decreased intracellular cholesterol accumulation and lowered TNF-a, IL-1β and IL-6 secretion in ox-LDL treated macrophages. Interestingly, further work found dioscin significantly reduced expression of LOX-1 and NF-κB in the aortic tissue and ox-LDL treated macrophages. In summary, our study was the first to confirm anti-atherosclerotic activity of dioscin in vivo and vitro. Moreover, the other important finding is dioscin mediated ox-LDL/LOX-1/NF-κB regulated contributions to the attenuate macrophage ox-LDL uptake and AS.

Cancer is the leading cause of morbidity and mortality worldwide, particularly lung cancer. Heat shock proteins and their upstream heat shock factors are involved in the occurrence of cancer and have been widely researched. However, the role of heat shock factor 2 (HSF2) in lung cancer remains unclear. In the present study, expression levels of HSF2 in lung cancer tissues from 50 lung cancer patients were detected by reverse transcription quantitative polymerase chain reaction, and 76% (38/50) were upregulated compared with the matched normal tissues. This suggested possible involvement of HSF2 in lung cancer. To additionally investigate the role of HSF2 in lung cancer occurrence, a plasmid encoding HSF2 was constructed. HSF2 was over expressed in normal lung epithelial BEAS-2B cells and lung cancer A549 cells. The results showed that HSF2 overexpression promoted cell proliferation and cell migration in BEAS-2B and A549 cells. Additional experiments showed that the HSF2-induced cell proliferation and cell migration were dependent on induction of HSPs, particularly HSP27 and HSP90, as co-transfection of HSP27 small interfering RNA (siRNA) or HSP90 siRNA attenuated HSF2-induced cell growth and migration. In conclusion, the present study showed that HSF2 is aberrantly expressed in lung cancer, and it may be an upstream regulator of HSPs, which may strongly affect cell growth and cell migration. Additional studies are required to explain the detailed mechanism between lung cancer, HSF2, HSPs and other possible signaling pathways.