[Transurethral resection of the prostate versus transurethral columnar balloon dilatation of the prostate in the treatment of benign prostatic hyperplasia].

OBJECTIVE: To compare the effects of transurethral resection of the prostate (TURP) and transurethral columnar balloon dilatation of the prostate (TUCBDP) in the treatment of BPH. METHODS: This study included 218 BPH patients treated in Qinhuangdao Workers' Hospital from July 2021 to November 2022, 109 by TURP and the other 109 by TUCBDP. We followed up the patients for 12 months, observed their postoperative recovery, complications, serum pain, inflammatory index, cytokine level, urodynamic index, symptom improvement and quality of life (QOL) and compared the data obtained between the two groups of patients. RESULTS: At 12 months after surgery, the total effectiveness rate was significantly higher in the TUCBDP than in the TURP group (93.58% vs 84.40%, P< 0.05), and the postoperative recovery was better in the former than in the latter (P< 0.05). Compared with the baseline, the levels of serum prostaglandin E2 (PGE2), substance P, tumor necrosis factor-alpha (TNF-α) and high sensitive C-reactive protein (hs-CRP) were remarkably increased in both of the groups on the first day after surgery (P< 0.05), more significantly in the TURP than in the TUCBDP group (P< 0.05), while the levels of serum PSA and E2 decreased and the T level elevated in all the patients at 3 months postoperatively (P< 0.05), more significantly in the TUCBDP than in the TURP group (P< 0.05). Before and at 3 and 12 months after operation, the postvoid residual urine volume (PVR) and NIH-CPSI, IPSS and QOL scores showed a decreasing trend, while the maximum urinary flow rate (Qmax), maximum cystometric capacity (MCC) and maximum urethral closure pressure (MUCP) exhibited an increasing trend in both of the two groups, even more significantly in the TUCBDP than in the TURP group (P< 0.05). CONCLUSION: TUCBDP is advantageous over TURP in promoting postoperative recovery, improving QOL, reducing postoperative pain, inflammation and complications, regulating the levels of serum cytokines, and improving urodynamics and clinical symptoms in BPH patients. However, with the extension of postoperative time, the two strategies are basically comparable in improving the urodynamics, symptoms and QOL of the patients.

Preparation of NIR-Responsive Gold Nanocages as Efficient Carrier for Controlling Release of EGCG in Anticancer Application.

Hepatocellular carcinoma (HCC) is a type of cancer that has a restricted therapy option. Epigallocatechin gallate (EGCG) is one of the main biologically active ingredients in tea. A large number of studies have shown that EGCG has preventive and therapeutic effects on various tumors. In addition, the development of near-infrared (NIR)-responsive nano-platforms has been attracting cancer treatment. In this work, we designed and synthesized a strategy of gold nanocages (AuNCs) as an efficient carrier for controlling release of EGCG for anti-tumor to achieve the synergistic functions of NIR-response and inhibited tumor cell proliferation. The diameter of AuNCs is about 50 nm and has a hollow porous (8 nm) structure. Thermal imaging-graphic studies proved that the AuNCs-EGCG obtained have photothermal response to laser irradiation under near-infrared light and still maintain light stability after multiple cycles of laser irradiation. The resulted AuNCs-EGCG reduced the proliferation rate of HepG2 cells to 50% at 48 h. Western blot analysis showed that NIR-responsive AuNCs-EGCG can promote the expression of HepG2 cell apoptosis-related proteins HSP70, Cytochrome C, Caspase-9, Caspase-3, and Bax, while the expression of Bcl-2 is inhibited. Cell confocal microscopy analysis proved that AuNCs-EGCG irradiated by NIR significantly upregulates Caspase-3 by nearly 2-fold and downregulates Bcl-2 by nearly 0.33-fold, which is beneficial to promote HepG2 cell apoptosis. This study provides useful information for the NIR-responsive AuNCs-EGCG as a new type of nanomedicine for HCC.

Prospects of NIR fluorescent nanosensors for green detection of SARS-CoV-2.

The pandemic of the novel coronavirus disease 2019 (COVID-19) is continuously causing hazards for the world. Effective detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can relieve the impact, but various toxic chemicals are also released into the environment. Fluorescence sensors offer a facile analytical strategy. During fluorescence sensing, biological samples such as tissues and body fluids have autofluorescence, giving false-positive/negative results because of the interferences. Fluorescence near-infrared (NIR) nanosensors can be designed from low-toxic materials with insignificant background signals. Although this research is still in its infancy, further developments in this field have the potential for sustainable detection of SARS-CoV-2. Herein, we summarize the reported NIR fluorescent nanosensors with the potential to detect SARS-CoV-2. The green synthesis of NIR fluorescent nanomaterials, environmentally compatible sensing strategies, and possible methods to reduce the testing frequencies are discussed. Further optimization strategies for developing NIR fluorescent nanosensors to facilitate greener diagnostics of SARS-CoV-2 for pandemic control are proposed.

Therapy of spinal cord injury by zinc modified gold nanoclusters via immune-suppressing strategies.

BACKGROUND: Spinal cord injury (SCI) is damage to the central nervous system (CNS) that causes devastating complications from chronic pain to breathing problems. Unfortunately, few effective and safe treatments are known to relieve the damages of SCI. Nanomedicines are used for the treatment of SCI with relatively few side effects, but only depending on the delivery of additional drugs, which increase complexity to the treatment. Considering the urgent need for saving SCI patients, it is important to develop promising nanobiotechnology for relieving their pains. METHODS: The clinical survey was used to investigate SCI patients, thereafter the therapy plan was designed. The receiver-operating characteristics (ROC) curves of the prediction model were built to find symptoms after SCI. The treatment plan (i.e. immunosuppressive strategy) was designed by manufacturing therapies based on gold nanoclusters (AuNCs). The response of the immune cells (macrophages) was studied accordingly. The western blot, reactive oxygen species (ROS) activity assay, enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (RT-qPCR), and immunochemical staining were used for evaluation of the in vivo and in vitro therapeutic effects. RESULTS: We found increased monocytes/macrophages (M/Ms) levels in 114 SCI subjects (44.7% with severe SCI complications) by the clinical survey. Additionally, the enhanced macrophage level was found to be closely related to the walking disorder after SCI. Since macrophages were central effector cells of the immune system, we assumed that the immune-suppressing strategies could be used for SCI therapy. Thereafter, AuNCs were stabilized by dihydrolipoic acid (DHLA) enantiomers (including DL-DHLA, R-DHLA; A racemic mixture (R and S) was denoted as DL; R and S refer to Rectus and Sinister), obtaining DL-DHLA-AuNCs and R-DHLA-AuNCs, respectively. In addition, zinc-modified DL-DHLA and R-DHLA stabilized AuNCs (i.e., DL-DHLA-AuNCs-Zn and R-DHLA-AuNCs-Zn) were investigated. Among these AuNCs, R-DHLA-AuNCs-Zn showed the most remarkable therapeutic effect for promoting the polarization of pro-inflammatory macrophages and reducing neuronal ROS-induced apoptosis and inflammation in vitro and in vivo; the lesion size was decreased and the survival rate of ventral neurons is higher. CONCLUSIONS: R-DHLA-AuNCs-Zn have comprehensive therapeutic capabilities, especially the immune-suppressing effects for the therapy of SCI, which is promising to relieve the pain or even recover SCI for the patients.

TNF promotes M1 polarization through mitochondrial metabolism in injured spinal cord.

Macrophages and microglia (M/Ms) in the injured spinal cord maintain a predominantly neurotoxic M1 phenotype that is disadvantageous to repair in the development of spinal cord injury (SCI). It has been reported that tumor necrosis factor (TNF) that polarize M/Ms toward M1 state in various disorders. In this study, we found that ablation of TNF endorsed the beneficial conversion from M1 to M2 phenotype and improved the mitochondrial metabolism in vivo and in vitro. In addition, PGC-1α that accumulates in TNF null mice, a major participant of mitochondrial metabolism, downregulated ROS activity and the expressions of M1-specific mRNA. Moreover, the absence of TNF upgraded the morphology and quantity of damaged mitochondria and rapidly switched to M2 phenotype as compare to administration of N-Acetyl-l-cysteine (NAC). Furthermore, systemic application of TPEN showed that increased ratio of M1 M/Ms. These combined results supporting predominant and prolonged TNF expression that is destructive to recovery after SCI. These results indicated that TNF would have great potential immunomodulatory for the treatment of SCI.

Knockdown of long non-coding RNA NEAT1 relieves the inflammatory response of spinal cord injury through targeting miR-211-5p/MAPK1 axis.

Spinal cord injury (SCI) is a refractory disease often accompanied by inflammation. Long non-coding RNA NEAT1 (lncRNA NEAT1) was reported to be involved in the expression of the inflammasomes, while the regulatory effect of NEAT1 on SCI was poorly investigated. Herein, we carried out further studies on the pathogenesis of SCI. PC-12 cells were incubated with lipopolysaccharide (LPS) to induce inflammation. Western blotting assay was used to measure the protein expression levels. RNA expression levels were analyzed using RT-qPCR. Cell counting kit 8 and flow cytometry assays were used to separately determine the cell viability and apoptosis rate. The targeted relationships were verified by luciferase reporter and RNA pull-down assays. It was found that LPS induced inflammation in the PC-12 cells, leading to significantly higher cell apoptosis rate and lower viability, and the expression level of NEAT1 was elevated by LPS. However, knockdown of NEAT1 partially reversed the effects of LPS. Subsequently, the potential interaction between NEAT1 and miR-211-5p was validated and miR-211-5p inhibitor was further confirmed to antagonize the effects of NEAT knockdown. The downstream target gene of miR-211-5p was predicted and verified to be MAPK1. In addition, overexpression of MAPK1 was proved to antagonize the effects of NEAT1 knockdown. Taken together, the knockdown of NEAT1 remarkably alleviated the inflammation of SCI via miR-211-5p/MAPK1 axis.

Total glucosides of paeony protects THP-1 macrophages against monosodium urate-induced inflammation via MALAT1/miR-876-5p/NLRP3 signaling cascade in gouty arthritis.

BACKGROUND: Monosodium urate (MSU)-mediated inflammatory response is a crucial inducing factor in gouty arthritis. Here, we explored the underlying mechanism of total glucosides of paeony (TGP) in MSU-induced inflammation of THP-1 macrophages in gouty arthritis. METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell viability. Enzyme-linked immunosorbent assay (ELISA) was utilized to measure the production of interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α). Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to determine RNA and protein expression. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay were used to confirm the interaction between miR-876-5p and MALAT1 or NLR family pyrin domain containing 3 (NLRP3). RESULTS: MSU-induced damage and inflammatory response in THP-1 macrophages were alleviated by the treatment of TGP in a dose-dependent manner. Overexpression of NLRP3 or MALAT1 reversed the protective effects of TGP in MSU-induced THP-1 macrophages. The binding relation between miR-876-5p and MALAT1 or NLRP3 was identified in THP-1 macrophages. MALAT1 up-regulated the expression of NLRP3 by sponging miR-876-5p in THP-1 macrophages. TGP suppressed MSU-induced inflammation in THP-1 macrophages through regulating MALAT1/miR-876-5p/NLRP3 axis. TGP suppressed MSU-induced activation of TLR4/MyD88/NF-κB pathway through regulating MALAT1/miR-876-5p/NLRP3 axis. CONCLUSION: In conclusion, TGP suppressed MSU-induced inflammation in THP-1 macrophages through regulating MALAT1/miR-876-5p/NLRP3 axis and TLR4/MyD88/NF-κB pathway, suggesting that TGP was a promising active ingredient for gouty arthritis treatment.

Whole Body Vibration Retards Progression of Atherosclerosis via Insulin-Like Growth Factor 1 in Apolipoprotein E-Deficient Mice.

Whole body vibration (WBV) has a marked impact on lipid metabolism and the endocrine system, which is related to the progression of atherosclerosis (AS). To investigate the effects of WBV, we measured the atherosclerotic plaque area of apolipoprotein E-knockout (ApoE-/-) AS mice, which were trained by WBV (15 Hz, 30 min) for 12 weeks. Simultaneously, serum levels of lipids, insulin-like growth factor 1 (IGF-1), insulin-like growth factor 1 receptor (IGF-1R), interleukin 6 (IL-6), and the mRNA and protein levels of the same in the aorta were compared between the control and WBV groups. The results indicated that WBV significantly reduced the atherosclerotic plaque area with lower very low-density lipoprotein (VLDL) and oxidized low-density lipoprotein (ox-LDL) in the blood. Moreover, the levels of IGF-1 in serum and expression of IL-6, IGF-1R, and p-IGF-1R protein in the mice aorta decreased significantly in the WBV group. In addition, we found that serum IGF-1 in mice increased to the highest concentration in 30 min after WBV for 10, 30, 60, and 120 minutes. These results suggested that appropriate WBV may delay the progression of AS, which was associated with acutely elevated serum IGF-1 and lower levels of IGF-1 and IL-6 in the aorta for long-term treatment.

Epothilone B impairs functional recovery after spinal cord injury by increasing secretion of macrophage colony-stimulating factor.

The microtubule-stabilizing drug epothilone B (epoB) has shown potential value in the treatment of spinal cord injury (SCI) through diverse mechanisms. However, it remains elusive why a limited overall effect was observed. We aim to investigate the limiting factors underlying functional recovery promoted by epoB. The same SCI model treated by epoB was established as discussed previously. We used a cerebrospinal fluid (CSF) sample to assess the changes in cytokines in milieu of the SCI lesion site after epoB treatment. We then analyzed the source of cytokines, the state of microglia/macrophages/monocytes (M/Ms), and the recruitment of neutrophil in the lesion site by using the results of antibody array. Following these findings, we further evaluated the motor functional recovery caused by the reshaped microenvironment. Systemic administration of epoB significantly increased levels of several cytokines in the CSF of the rat SCI model; macrophage colony-stimulating factor (M-CSF) secreted by intact central nervous system (CNS) cells was one of the cytokines with increased levels. Along with epoB and other cytokines, M-CSF reshapes the SCI milieu by activating the microglias, killing bone marrow-derived macrophages, polarizing the M/M to M1 phenotype, and activating downstream cytokines to exacerbate the SCI injury, but it also increases the expression of neurotrophic factors. Anti-inflammatory therapy using a neutralizing antibody mix shows encouraging results. Using in vivo experiments, our findings indicate that epoB inhibits the SCI functional recovery in many ways by reshaping the milieu, which counteracts the therapeutic efficacy that led to the limited overall effectiveness.

Activation of the Nrf2/ARE signaling pathway by probucol contributes to inhibiting inflammation and neuronal apoptosis after spinal cord injury.

The nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays an essential role in the cellular antioxidant and anti-inflammatory responses. Spinal cord injury (SCI) results in a massive release of inflammatory factors and free radicals, which seriously compromise nerve recovery and axon regeneration. In this study, we examined the efficacy of probucol on anti-inflammatory responses and functional recovery after SCI by activating the Nrf2/ARE signaling pathway. We also investigated the mechanism by which inflammation is inhibited in this process. We found that treatment of injured rats with probucol significantly increased levels of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase-1 (NQO1), while levels of inflammatory cytokines, interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were decreased. This was associated with a reduction in neural cell apoptosis and promotion of nerve function recovery. These results demonstrate that the neuroprotective effects of probucol after SCI are mediated by activation of the Nrf2/ARE signaling pathway. These findings indicate that the anti-inflammatory effects of probucol represent a viable treatment for improving functional recovery following SCI.

KLF15 regulates dopamine D2 receptor and participates in mouse models of neuropathic pain.

Neuropathic pain is caused by damage to the nervous system, resulting in aberrant pain. The mechanism underlying neuropathic pain remains largely unknown. Krüppel-like factor 15 (KLF15) is a member of the Krüppel-like factor family of transcriptional factors. Here in this study, we aimed to investigate the potential role of the transcriptional factor KLF15 in neuropathic pain. The mRNA and protein levels of Klf15 were significantly increased in the neurons of mouse undergoing neuropathic pain induced by sciatic nerve chronic constrictive injury (CCI) or unilateral spared nerve injury (SNI). In neurons, the upregulation of Klf15 was triggered by the inflammatory factor tumor necrosis factor alpha (TNF-α). As a transcriptional factor, KLF15 promoted the expression of dopamine D2 receptor (Drd2), which is a receptor essentially involved in neuropathic pain. KLF15 bound to the promoter of Drd2 directly and promoted the promoter activity of Drd2. Finally, we showed that knockout of Klf15 repressed the sensitivity in neuropathic pain induced by CCI or SNI. In conclusion, KLF15 is induced in neuropathic pain via a TNF-α-dependent manner and contributes to neuropathic pain partially through promoting the expression of dopamine D2 receptor.

Astragalus polysaccharides inhibits cell growth and pro-inflammatory response in IL-1ß-stimulated fibroblast-like synoviocytes by enhancement of autophagy via PI3K/AKT/mTOR inhibition.

The hyperplastic growth of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and inflammatory response are pathological hallmarks of RA. It has been reported that Astragalus polysaccharides (APS) possess appreciable anti-inflammatory activity against adjuvant-induced arthritis. Nevertheless, little is known about the role and detailed mechanism underlying the therapeutic effects of APS in RA. This study demonstrated that administration of APS dose-dependently impaired cell viability, increased cell apoptosis by decreasing Bcl-2 expression, increasing Bax expression and Caspase3 activity in IL-1ß-stimulated RSC-364 cells and RA-FLS. Simultaneously, IL-1ß-induced production of pro-inflammatory cytokines IL-6 and TNF-α was significantly decreased after APS treatment. Furthermore, preconditioning with APS dramatically enhanced autophagy activity by increasing Beclin-1 and LC3II/LC3I expression coupled with decreasing p62 expression and augmenting the number of LC3 puncta in IL-1ß-stimulated RSC-364 cells. More importantly, autophagy inhibitor 3-methyladenine (3-MA) partly abolished APS-triggered inhibitory effects on cell growth and production of pro-inflammatory cytokines. APS also repressed the activation of PI3K/Akt/mTOR signaling pathway in IL-1ß-stimulated RSC-364 cells. Moreover, treatment with insulin-like growth factor-1 (IGF-1), an activator of PI3K/Akt signaling, partly reversed the therapeutic effects of APS in IL-1ß-stimulated RSC-364 cells. Collectively, we concluded that APS might attenuate the pathological progression of RA by exerting the pro-apoptotic and anti-inflammatory effects in IL-1ß-stimulated FLSs by regulating the PI3K/AKT/mTOR-autophagy pathway.

Resveratrol protects against spinal cord injury by activating autophagy and inhibiting apoptosis mediated by the SIRT1/AMPK signaling pathway.

Spinal cord injury (SCI) is a devastating condition with few effective treatments. Resveratrol, a polyphenolic compound, has exhibited neuroprotective effects in many neurodegenerative diseases. However, the explicit effect and mechanism of resveratrol on SCI is still unclear. Adenosine 5' monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1), the downstream protein, play key roles in metabolizing of energy, resisting of resistance, and cellular protein homeostasis. In this study, we determined the effects of resveratrol on SCI and their potential relationship with SIRT1/AMPK signaling pathway, autophagy and apoptosis. To determine the effect of resveratrol on SCI recovery, a spinal cord contusion model was employed. Rats received treatment with resveratrol or DMSO immediately following contusion. We determined that Basso, Beattie, and Bresnahan (BBB) scores were significantly higher for injured rats treated with resveratrol. Nissl and HE staining revealed that resveratrol treatment significantly reduced the loss of motor neurons and lesion size in the spinal cord of injured rats when compared to vehicle-treated animals. Spinal cord tissue was assessed by Western blot, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analyses 7days after injury for changes in expression of SIRT1/AMPK signaling pathway, autophagy and apoptosis proteins. Expression of SIRT1, p-AMPK, Beclin-1, LC3-B, and Bcl-2 was elevated in resveratrol-treated animals, whereas expression of p62, Cleaved Caspase-3, Caspase-9, and Bcl-2 associated X protein (Bax) was inhibited. Immunofluorescence analysis of primary neurons treated with resveratrol alone or in combination with Compound C (AMPK inhibitor) or EX527 (SIRT1 inhibitor) revealed that treatment with the inhibitors blocks the increased LC3-B expression in cells and increases the portion of TUNEL-positive cells. Taken together, these results suggest that resveratrol exerts neuroprotective effects on SCI by regulating autophagy and apoptosis mediated by the SIRT1-AMPK signaling pathway.