Engineering naphthalimide-cyanine integrated near-infrared dye into ROS-responsive nanohybrids for tumor PDT/PTT/chemotherapy.

Photodynamic (PDT) and photothermal therapies (PTT) are emerging treatments for tumour ablation. Organic dyes such as porphyrin, chlorin, phthalocyanine, boron-dipyrromethene and cyanine are the clinically or preclinically used photosensitizer or photothermal agents. Development of structurally diverse near-infrared dyes with long absorption wavelength is of great significance for PDT and PTT. Herein, we report a novel near-infrared dye ML880 with naphthalimide modified cyanine skeleton. The introduction of naphthalimide moiety results in stronger electron delocalization and larger redshift in emission compared with IR820. Furthermore, ML880 is co-loaded with chemotherapeutic drug into ROS-responsive mesoporous organosilica (RMON) to construct nanomedicine NBD&ML@RMON, which exhibits remarkable tumor inhibition effects through PDT/PTT/chemotherapy in vivo.

The Efficacy and Safety of Extracorporeal Shockwave Therapy versus Acupuncture in the Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Evidence Based on a Network Meta-analysis.

The aim of this study was to evaluate the efficacy and safety of extracorporeal shockwave therapy (ESWT) and acupuncture therapy for patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).We searched electronic databases including PubMed, Cochrane Library, Embase and web of science from its inception to June 1, 2021. The randomized controlled trials (RCTs) that compared ESWT and acupuncture in the management of CP/CPPS were identified. A network meta-analysis was conducted with the software of STATA 14.0.Nine RCTs with 525 patients were enrolled in our analysis. The results revealed that both ESWT and acupuncture were significantly better than the sham procedure in the outcomes of total score of NIH-CPSI, pain subscore, urinary symptoms subscore, QoL subscore, IPSS score, the IIEF score and response rates (p < .05). Both ESWT and acupuncture were well-tolerated and had no obviously increased adverse events. Compared with acupuncture, ESWT was associated with better short term (<4w) and mid-term (8-12 w) efficacy of total score, pain subscore, urinary symptoms subscore, and QoL subscore of NIH-CPSI, IPSS score, IIEF score, and response rate. However, ESWT did not present better long-term (<24 w) outcomes than acupuncture in total score, pain subscore, urinary symptoms subscore, and QoL subscore of NIH-CPSI.Both ESWT and acupuncture were effective and well-tolerated in the management of CP/CPPS. ESWT seemed to have better short (<4 w) and mid-term (8-12 w) efficacy but similar long-term (>24 w) efficacy than acupuncture.

Genistein-3'-sodium sulfonate ameliorates cerebral ischemia injuries by blocking neuroinflammation through the α7nAChR-JAK2/STAT3 signaling pathway in rats.

BACKGROUND: Neuroinflammation plays a pivotal role in the acute progression of cerebral ischemia/reperfusion injury (I/RI). We previously reported that genistein-3'-sodium sulfonate (GSS), a derivative from the extract of the phytoestrogen genistein (Gen), protects cortical neurons against focal cerebral ischemia. However, the molecular mechanism underlying the neuroprotective effects exerted by GSS remains unclear. PURPOSE: The present study focused on the anti-inflammatory effects of GSS following I/RI in rats. STUDY DESIGN: Randomized controlled trial. METHODS: The tMCAO rat model and LPS-stimulated BV2 in vitro model were used. Longa's scare was used to observe neurological function. TTC staining and Nissl staining were used to evaluate brain injury. ELISA, qRT-PCR, Western blotting and immunofluorescent staining methods were used to detect cytokine concentration, mRNA level, protein expression and location. RESULTS: GSS treatment improves neurological function, reduces the volume of cerebral infarction, attenuates proinflammatory cytokines and inactivates the phosphorylation of JAK2 and STAT3 in I/RI rats. Furthermore, GSS increased the expression of α7nAChR. More importantly, the neuroprotective, anti-inflammatory and inhibiting JAK2/STAT3 signaling pathway effects of GSS were counteracted in the presence of alpha-bungarotoxin (α-BTX), an α7nAChR inhibitor, suggesting that α7nAChR is a potential target associated with the anti-inflammatory effects of GSS in the I/RI rats. GSS also inhibited BV2 cells from releasing IL-1ß via the α7nAChR pathway after LPS stimulation. CONCLUSION: GSS protects against cerebral I/RI through the expression of α7nAChR and inhibition of the JAK2/STAT3 pathway. Our findings provide evidence for the role of the cholinergic anti-inflammatory pathway in neuroinflammation and uncover a potential novel mechanism for GSS treatment in ischemic stroke. The downstream signals of GSS, α7nAChR- JAK2/STAT3 could also be potential targets for the treatment of I/RI.

Inhibitory effects of citrus lemon oil and limonene on Streptococcus sobrinus - Induced dental caries in rats.

OBJECTIVE: This study aimed to examine and compare the anti-caries effects of citrus lemon oil (CLO) and limonene in rats. METHODS: The minimal inhibitory concentrations of CLO and limonene were measured using the disk diffusion method. The rats were infected with Streptococcus sobrinus and assigned into four groups: (1) Chlorhexidine, (2) CLO, (3) limonene, and (4) distilled water (H2O). The total cultivable microbiota and Streptococcus sobrinus in the mouth of the rats were counted, and the caries lesions were measured by Keyes' scoring and DIAGNOdent examination. RESULTS: The minimal inhibitory concentrations of CLO and limonene against Streptococcus sobrinus were 4.50 and 21.00 mg/mL, respectively. The chlorhexidine group had the lowest total microbiota counts (p < 0.05), while there were no significant differences among the CLO, limonene and H2O groups (p > 0.05). The proliferation of Streptococcus sobrinus was remarkably inhibited by chlorhexidine, limonene and CLO (p < 0.05). The Keyes' scoring and DIAGNOdent results indicated that the caries lesions were reduced in the CLO and limonene groups compared to that of the vehicle control group (p < 0.05). There was no significant difference between CLO and limonene (p > 0.05). CONCLUSION: Limonene and CLO have similar anti-caries abilities in a bacteriostatic manner in vivo.

Effects of lemon essential oil and limonene on the progress of early caries: An in vitro study.

OBJECTIVE: The purpose of this study was to investigate the effects of Lemon essential oil (LEO) and Limonene (LIM) in the progress of early caries. DESIGN: LEO and LIM were selected as experimental medicine, while sodium fluoride (NaF) and deionized water (DW) were positive and blank controls, respectively. Bovine incisors were used to establish enamel and dentin early caries models by demineralization method in vitro. Then specimens were subjected to pH cycling. Calcium and phosphate release of demineralizing solution were measured by an automatic biochemical analyzer; Surface microhardness tester and energy dispersive X-ray spectrometer were used to detect the surface microhardness recovery and calcium- phosphate ratio on tooth surface; Degraded collagen matrix by collagenase was investigated by assaying hydroxyproline. RESULTS: Calcium release of dentin demineralizing solution of LEO group was lower than DW group's and higher than NaF group's. Both of LEO and LIM groups, the surface microhardness recovery were significantly lower than those of NaF group, which were similar to DW group. Dentin surface calcium- phosphate ratio of LEO and LIM groups were lower than those of NaF group and higher than those of DW group. Hydroxyproline concentration in the remineralizing solution of LEO and LIM groups were lower than DW groups' and higher than NaF groups'. CONCLUSIONS: LEO and LIM have influence on the progress of dentin early caries, which can stabilize its structure by inhibiting collagen degradation. Meanwhile, these medicines may provide a new drug choice for the prevention and treatment of early root caries.

Ginkgo biloba extract in combination with sorafenib is clinically safe and tolerable in advanced hepatocellular carcinoma patients.

BACKGROUND: Sorafenib is the only therapy shown to improve overall survival in advanced hepatocellular carcinoma (HCC). However, the clinical efficacy of sorafenib is limited. Combination therapy targeting multiple signaling pathways may improve outcomes. Ginkgo biloba extract (GBE) has exhibited antitumor activity in multiple human cancers. HYPOTHESIS/PURPOSE: This study was designed to evaluate the tolerability and effectiveness of GBE combined with sorafenib in patients with advanced HCC. STUDY DESIGN: Patients with advanced HCC were treated with increasing doses of GBE in combination with sorafenib. METHODS: We first determined the maximum tolerated dose (MTD) of GBE, then the patients were treated with GBE at the MTD to evaluate its safety and efficacy. 27 patients were enrolled in the first part of our study and treated with sorafenib 400mg twice daily (BID) and increasing doses (cohort 1: 60mg, cohort 2: 120mg, cohort 3: 240mg, cohort 4: 360mg) of GBE once daily (QD). An additional group of 32 new patients next to the 27 described before were accrued for the second part of our study, and all these 32 patients were eligible for the evaluation of toxicity and efficacy. RESULTS: No patient in cohort 1 and 2 experienced a dose-limiting toxicity (DLT). One of the ten patients in cohort 3 experienced a DLT. DLT occurred in two of the three initial patients in cohort 4. Cohort 3 (GBE 240mg QD plus sorafenib 400mg BID) was considered to be the MTD. Three patients had a partial response, 21 had stable disease, and 8 had progressive disease. The median times to progression and overall survival were 2.5 and 11.6 months, respectively. Compared with previous study, the toxicities of the combination therapy were similar with those observed in sorafenib monotherapy, GBE in combination with sorafenib slightly improved OS. CONCLUSIONS: The combination of GBE (240mg QD) and standard dose sorafenib (400mg BID) is safe and tolerable among patients with advanced HCC. Early signs of antitumor activity may warrant further development of this combination.