The morbidity and mortality of prostate cancer are increasing year by year, and the survival rate of prostate cancer patients after treatment is low. Therefore, investigating the molecular mechanism underlying prostate cancer is crucial for developing effective treatments. Recent studies have shown the important role of long-chain non-coding RNAs (lncRNAs) in tumorigenesis. VPS9D1-AS1 can modulate the progression of multiple cancers, but its molecular action mechanism in prostate cancer remains unknown. This study, therefore, intended to investigate the regulatory mechanism of VPS9D1-AS1 in prostate cancer. First, differentially expressed lncRNAs in prostate cancer were identified through bioinformatics approaches. The target lncRNA for the study was determined by reviewing the relevant literature and its downstream miRNA/mRNA axis was uncovered. Then, quantitative reverse transcription polymerase chain reaction was introduced to assess the expression of VPS9D1-AS1, miR-187-3p, and fibroblast growth factor receptor-like 1 (FGFRL1) at a cellular level, and Western blot was conducted to assess the protein level of FGFRL1 in cells. The results indicated that VPS9D1-AS1 and FGFRL1 were highly expressed in prostate cancer while miR-187-3p was less expressed. Besides, MTT, colony formation, wound healing, and cell invasion assays showed that silencing VPS9D1-AS1 inhibited the viability, migration ability, and invasion ability of prostate cancer cells. Dual-luciferase assay and RNA binding protein immunoprecipitation assay were performed to explore the interplay of miR-187-3p and VPS9D1-AS1 or FGFRL1. The results showed that VPS9D1-AS1 could sponge miR-187-3p, and FGFRL1 could serve as a direct target of miR-187-3p. Moreover, combined with the results of the rescue experiment, VPS9D1-AS1 was found to upregulate FGFRL1 by competitively sponging miR-187-3p to accelerate the malignant behaviors of prostate cancer cells. In conclusion, VPS9D1-AS1 could promote the phenotype progression of prostate cancer cells through targeting the miR-187-3p/FGFRL1 axis, and it has the potential to be a target for prostate cancer patients.

Acute cardiomyopathy is a significant global health concern and one of the leading causes of death in developed countries. Prior studies have shown an association between acute cardiomyopathy and low vitamin D levels. Although paricalcitol, a vitamin D receptor (VDR) activator, has demonstrated clinical benefits in patients with advanced kidney disease, its effect on cardiac remodeling in cardiomyopathy is unknown. This study aimed to investigate the relative effects of paricalcitol on cardiomyopathy in rats. Wistar–Kyoto rats were administered vehicle (sham control group) or isoproterenol to induce cardiomyopathy. Rats administered isoproterenol were subsequently treated with paricalcitol (experimental group) or vehicle (isoproterenol group). Picrosirius red and immunofluorescence staining were used to analyze cardiac fibrosis and hypertrophy. Immunohistochemistry staining was used to confirm the molecular mechanisms involved in isoproterenol-induced cardiomyopathy in rats. Injection of paricalcitol could reduce collagen and transforming growth factor-beta 1 (TGF-β1) levels while activating fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor-23 (FGF23) without the help of Klotho, thereby reducing myocardial hypertrophy and fibrosis. As a VDR activator, paricalcitol reduces isoproterenol-induced cardiac fibrosis and hypertrophy by reducing the expression of TGF-β1 and enhancing the expression of VDR, FGFR1, and FGF23.

The flowers of daylily (Hemerocallis fulva Linn.) have been used as vegetable and medicinal herb for thousands of years in Taiwan and eastern Asia. Daylily flowers have been demonstrated to exert several biomedical properties. In this study, we provided the evidences show that daylily flowers exert anti-inflammatory activity in vitro and improved the sleep quality in vivo. We demonstrated that adult volunteers received water extract of daylily flowers improved sleep quality, sleep efficiency and daytime functioning, while sleep latency was reduced, compared to the adult volunteers received water. In addition, we demonstrated that aqueous and ethanol extracts of daylily flowers inhibited nitric oxide and interleukin-6 production in lipopolysaccharide-activated macrophages. Furthermore, the quantitative high performance liquid chromatography-based analysis showed the rutin content of the aqueous extract, ethanolic extract, ethyl acetate fractions of ethanolic extract, and water fractions of ethanolic extract were 7.27, 23.30, 14.71, and 57.43 ppm, respectively. These results indicate that daylily flowers have the potential to be a nutraceutical for improving inflammatory-related diseases and sleep quality in the future.

Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder, and there is an association between it and the development of cardiovascular disease. The aim of this study was to explore whether there is a glutamatergic pathway connecting the medial habenula (MHb) with the rostral ventrolateral medulla (RVLM) that is involved in the regulation of cardiovascular function in a rat model of PTSD. Vesicular glutamate transporter 2 (VGLUT2)-positive neurons in the MHb region were retrogradely labeled with FluoroGold (FG) by the double-labeling technique of VGLUT2 immunofluorescence and FG retrograde tracing. Rats belonging to the PTSD model group were microinjected with artificial cerebrospinal fluid (ACSF) or kynurenic acid (KYN; a nonselective glutamate receptor blocker) into their RVLM. Subsequently, with electrical stimulation of MHb, the discharge frequency of the RVLM neurons, heart rate, and blood pressure were found to be significantly increased after microinjection of ACSF using an in vivo multichannel synchronous recording technology; however, this effect was inhibited by injection of KYN. The expression of N-methyl-D-aspartic acid (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits was significantly increased in RVLM of PTSD model rats analyzed by the Western blotting technique. These findings suggest that there may be a glutamatergic pathway connection between MHb and RVLM and that this pathway may be involved in the regulation of cardiovascular function in the PTSD model rats, by acting on NMDA and AMPA receptors in the RVLM.

Acute lung injury is a severe clinical condition constituting a major cause of mortality in intensive care units. This study aimed to investigate the role of klotho in alleviating lipopolysaccharide (LPS)-induced acute lung injury. LPS-induced acute lung injury was used to simulate the acute lung injury caused by severe pneumonia in vitro. The viability and apoptosis of A549 cells were detected by cell counting kit-8 assay and flow cytometry. The inflammatory response, oxidative stress, and mitochondrial function in A549 cells were analyzed by commercial assay kits and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl carbocyanine iodide (JC-1) staining. The expression of apoptosis-related proteins, Sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway-related proteins, and NOD-like receptor family pyrin domain containing 3 (NLRP3) expression in A549 cells was detected by western blot. The mtDNA synthase level in A549 cells was analyzed by reverse transcription-quantitative polymerase chain reaction. The results showed that, klotho had no cytotoxic effect on A549 cells. The viability and mitochondrial function were inhibited and apoptosis, inflammatory response, and oxidative stress were aggravated in LPS-induced A549 cells, which were all reversed by klotho. Klotho activated the SIRT1/Nrf2 signaling pathway to inhibit the LPS-induced NLRP3 inflammasome activation in A549 cells. However, EX527, a SIRT1 inhibitor, attenuated the klotho effect to suppress viability and mitochondrial function and promoted apoptosis, inflammatory response, and oxidative stress of A549 cells. In conclusion, klotho inhibited the activation of NLRP3 inflammasome to alleviate LPS-induced inflammatory injury of A549 cells and restore mitochondrial function through activating the SIRT1/Nrf2 signaling pathway.

The objective of this study was to examine the difference in sensory-motor impairments (i.e., balance, contracture, coordination, strength, spasticity, and sensation) between legs in children with hemiplegic cerebral palsy. An observational study measured both lower limbs of children with hemiplegic cerebral palsy over one session. Six sensory-motor impairments (balance, coordination, strength, spasticity, contracture, and proprioception) were measured. The between-leg differences were analyzed using the paired t-tests and presented as the mean differences (95% confidence interval (CI)). Twenty-four participants aged 10.3 years (standard deviation: 1.3) participated. The affected leg was less than the less-affected leg in terms of the strength of dorsiflexors (mean difference (MD) -2.8 Nm, 95% CI −4.2 to −1.4), plantarflexors (MD -2.6 Nm, 95% CI −4.1 to −1.0), knee extensors (MD -5.3 Nm, 95% CI −10.2 to −0.5) as well as range of ankle dorsiflexion (MD -8 deg, 95% CI −13 to −3), and balance (median difference -11.1, 95% CI −11.6 to −10.6). There was a trend toward a difference in terms of the strength of hip abductors (MD -2.6 Nm, 95% CI −5.3 to 0.1) and coordination (MD -0.20 taps/s, 95% CI −0.42 to 0.01). The legs were similar in terms of the strength of hip extensors (MD 0.3 Nm, 95% CI -4.7 to 5.3), proprioception (MD 1 deg, 95% CI 0 to 2), and spasticity (median difference 0, 95% CI 0 to 0). Examination of the difference in sensory-motor impairments between legs in children with hemiplegic cerebral palsy has given us some insights into the deficits in both legs. Not only was balance, strength, and coordination decreased compared with the less-affected leg but also the less-affected leg was markedly decreased compared with typically developing children. Therefore, an intervention aimed at increasing muscle strength and coordination in both legs might have a positive effect, particularly on more challenging physical activities. This may, in turn, lead to successful participation in mainstream sport and recreation.

Aging, a crucial risk factor for ischemic heart disease, has negative impacts on cardioprotective mechanisms. As such, there is still an unmet requirement to explore potential therapies for improving the outcomes of myocardial ischemia/reperfusion (IR) injury in elderly subjects. Here, we aimed to confirm the cardioprotective function of irisin/Dendrobium nobile Lindl (DNL) combination therapy against myocardial IR injury in aged rats, with a focus on the involvement of pyroptosis and mitophagy. Male aged Wistar rats (22–24 months old, 400–450 g; n = 54) underwent myocardial IR or sham surgery. Before IR operation, rats were pretreated with irisin (0.5 mg/kg, intraperitoneally) and/or DNL (80 mg/kg, orally) for 1 or 4 weeks, respectively, at corresponding groups. Cardiac function, lactate dehydrogenase (LDH) and cardiac-specific isoform of troponin-I (cTn-I) levels, the expression of proteins involved in pyroptosis (nod-like receptor protein-3 (NLRP3), apoptosis-associated speck-like protein, c-caspase-1, and GSDMD-N) and mitophagy (PINK1 and Parkin), and pro-inflammatory cytokines levels were evaluated after 24 h of reperfusion. Irisin/DNL combined therapy significantly restored cardiac function and decreased LDH and cTn-I levels. It also downregulated pyroptosis-related proteins, upregulated PINK1 and Parkin, and decreased pro-inflammatory cytokines secretion. Pretreatment with Mdivi-1, as mitophagy inhibitor, abolished the cardioprotective action of dual therapy. This study revealed the cardioprotective effects of irisin/DNL combination therapy against IR-induced myocardial injury in aged rats, and also showed that the mechanism might be associated with suppression of NLRP3-related pyroptosis through enhancing the activity of the PINK1/Parkin mitophagy. This combination therapy is worthy of further detailed studies due to its potential to alleviate myocardial IR injury upon aging.

As previously demonstrated, serum beta-human chorionic gonadotropin (β-hCG) is linked to identifying early gestational abnormalities. This research was aimed at investigating the correlation between serum β-hCG levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum (HG). Ninety-one pregnant women with HG were selected as the study group and divided into early pregnancy (EP), mid-pregnancy (MP), and late pregnancy (LP) groups according to their gestational weeks, while 84 normal pregnant women were selected as the control group. Venous blood was collected from pregnant women in both groups and serum β-hCG levels were measured by chemiluminescent immunoassay. The levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb), and thyroglobulin antibody (TgAb) were tested by chemiluminescent microparticle immunoassay. Visual analog scale (VAS) scores were utilized to assess the degree of HG. Pearson analysis was implemented to measure the correlations between serum β-hCG levels and serum FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and the correlations between β-hCG, FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and gestation period. The receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic values of thyroid hormones, thyroid-related antibodies, and β-hCG levels for HG. Versus those in the control group, β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores were higher and TSH levels were lower in the study group. Versus those in the EP group, β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women in the MP and LP groups were decreased, and TSH levels were increased. Serum β-hCG levels of pregnant women with HG were positively correlated with FT3, FT4, TPOAb, TRAb, TgAb, and VAS scores and negatively correlated with TSH levels. Serum β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women with HG had a negative correlation with the gestation period, while TSH levels had a positive correlation with the gestation period. The ROC curve analysis showed that β-hCG and thyroid function-related indicators were of high clinical values in the diagnosis of HG. Collectively, our article suggests that serum β-hCG expression of pregnant women with HG is abnormally elevated and closely related to the degree of HG and hyperthyroidism. In addition, β-hCG and thyroid function-related indicators have certain diagnostic efficacy for HG.

Colorectal cancer (CRC) is a cancer that occurs in the rectum or colon with a high incidence. Sperm-associated antigen 5 (SPAG5), a gene that regulates cell division, has been observed highly expressed in a variety of cancers, but its role in CRC is unclear. This study aimed to investigate the regulatory role of SPAG5 in CRC. The expression of SPAG5 in multiple cancers and normal tissues was predicted by The Cancer Genome Atlas and Tumor Immune Estimation Resource, and the expression of SPAG5 in human normal intestinal epithelial cells NCM460 and human CRC cell lines Caco2, HT29, SW480, and LOVO was verified by western blotting (WB). The effects of silencing SPAG5 on cell viability, proliferation, and apoptosis were then investigated by cell counting kit-8, WB, and flow cytometry. The effects of silencing SPAG5 on cell migration and invasion were investigated by scratch assay and transwell assay. Finally, the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and AKT in cells were detected by WB. The results showed that SPAG5 was highly expressed in CRC and was verified by WB. Silencing of SPAG5 inhibited cell viability and proliferation and increased the cell apoptosis rate. Furthermore, both cell invasion and migration abilities were suppressed by the low expression of SPAG5. Finally, WB results found that the phosphorylation levels of PI3K and AKT were reduced after SPAG5 silencing. In summary, the results showed that SPAG5 can promote the proliferation and invasion of CRC cells by targeting the PI3K/AKT signaling pathway.

Cervical cancer leads to 300,000 deaths annually and the mechanism of cervical carcinogenesis remains unclear. Zeste White 10-interacting kinetochore protein (ZWINT) is uniquely elevated in malignancies, promoting proliferation, migration, and colony formation of cancer cells. To investigate the role of ZWINT in proliferation, migration, invasion of cervical cancer, and evaluate the potential ability of ZWINT as a therapeutic target. First, ZWINT expression in cervical cancer was analyzed using the bioinformatic methods and assessed in several cervical cancer cell lines. The cell viability and colony formation assays were used to evaluate cell proliferation. Then, transwell assay was performed to investigate cell migration and invasion. Moreover, western blot was used to measure the expression level of ZWINT, matrix metalloproteinase 9 (MMP-9), N-cadherin, E-cadherin, p53 and p21 in CaSki and HeLa cells with ZWINT overexpression or knockdown. The bioinformatic analysis and western blot assay revealed the expression of ZWINT was significantly increased in cervical cancer. The cell viability and colony formation analysis illustrated that cell proliferation could be promoted by ZWINT overexpression and suppressed by ZWINT knockdown. Moreover, ZWINT promoted migration and invasion of CaSki and HeLa cells, through regulating the expression of MMP-9, N-cadherin, and E-cadherin. Furthermore, ZWINT attenuated the expression of p53 and p21 in cervical cancer cells. In summary, ZWINT functions in promoting cell proliferation, migration, and invasion of cervical cancer cells by suppressing p53/p21 signaling pathway, which indicated ZWINT is a potential therapeutic target for cervical cancer treatment.

Prostate cancer (PCa) is a common cancer and the leading cause of cancer-related death in men. To investigate the role of pre-mRNA processing factor 19 (PRPF19) in proliferation, migration of PCa, and evaluate the potential ability of PRPF19 as a therapeutic target. PRPF19 expression was analyzed from The Cancer Genome Atlas and GEPIA databank. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate the transcription of PRPF9 and solute carrier family 40 member 1 (SLC40A1). Immunohistochemistry (IHC) was used to test PRPF9 expression in PCa tissues. The cell viability and 5-ethynyl-2′-deoxyuridine incorporation analysis were performed to assess cell proliferation. Transwell assay was performed to investigate the migration and invasion of cancer cells. Western blot was used to measure the expression level of PRPF9, E-cadherin, Vimentin and α-smooth muscle actin (α-SMA), SLC40A1, LC3, Beclin-1 and ATG7. Immunofluorescence assay was performed to measure LC3 expression in PCa cells. The bioinformatic analysis revealed PRPF19 was highly expressed in PCa which was certified by qRT-PCR, western blot and IHC detection in PCa tissues. The proliferation of PCa cells could be promoted by PRPF19 overexpression and suppressed by PRPF19 knockdown. Moreover, the migration and invasion of PCa cells could be positively regulated by PRPF19 which promoted the expression of E-cadherin, Vimentin, and α-SMA. Furthermore, the expression of LC3, Beclin-1, and ATG7 was negatively regulated by PRPF19, indicating that PRPF19 inhibited autophagy in PCa cells. In the double knockdown of PRPF19 and SLC40A1, PRPF19 repressed the mRNA and reduced protein level of SLC40A1, and SLC40A1 antagonized effects of PRPF19 on proliferation, migration and autophagy of PCa cells. PRPF19 promoted proliferation and migration, and inhibited autophagy in PCa by attenuating SLC40A1 expression, indicating PRPF19 was a potential therapeutic target for PCa treatment.

Pancreatic cancer (PC) is one of the deadliest malignancies. Partner of NOB1 homolog (PNO1) has been reported to be involved in tumorigenesis. However, the role of PNO1 in PC remains to be elucidated. The purpose of this study was to examine the effects of PNO1 on the progression of PC and the possible mechanism related to E2F transcription factor 1 (E2F1), a transcription factor predicted by the JASPAR database to bind to the PNO1 promoter region and promoted the proliferation of pancreatic ductal adenocarcinoma. First, PNO1 expression in PC tissues and its association with survival rate were analyzed by the Gene Expression Profiling Interactive Analysis database. Western blot and reverse transcription-quantitative polymerase chain reaction were used to evaluate PNO1 expression in several PC cell lines. After PNO1 silencing, cell proliferation, migration, and invasion were measured by colony formation assay, 5-ethynyl-2'-deoxyuridine staining, wound healing, and transwell assays. Then, the lipid reactive oxygen species in PANC-1 cells was estimated by using C11-BODIPY^581/591 probe. The levels of glutathione, malondialdehyde, and iron were measured. The binding between PNO1 and E2F1 was confirmed by luciferase and chromatin immunoprecipitation (ChIP) assays. Subsequently, E2F1 was overexpressed in PANC-1 cells with PNO1 knockdown to perform the rescue experiments. Results revealed that PNO1 was highly expressed in PC tissues and PNO1 expression was positively correlated with overall survival rate and disease-free survival rate. Significantly elevated PNO1 expression was also observed in PC cell lines. PNO1 knockdown inhibited the proliferation, migration, and invasion of PANC-1 cells. Moreover, ferroptosis was promoted in PNO1-silenced PANC-1 cells. Results of luciferase and ChIP assays indicated that E2F1 could bind to PNO1 promoter region. Rescue experiments suggested that E2F1 overexpression reversed the impacts of PNO1 depletion on the malignant behaviors and ferroptosis in PANC-1 cells. Summing up, PNO1 transcriptionally activated by E2F1 promotes the malignant progression and inhibits the ferroptosis of PC.