Drug repurposing-based nanoplatform via modulating autophagy to enhance chemo-phototherapy against colorectal cancer.

Multi-modal combination therapy is regarded as a promising approach to cancer treatment. Combining chemotherapy and phototherapy is an essential multi-modal combination therapy endeavor. Ivermectin (IVM) is a potent antiparasitic agent identified as having potential antitumor properties. However, the fact that it induces protective autophagy while killing tumor cells poses a challenge to its further application. IR780 iodide (IR780) is a near-infrared (NIR) dye with outstanding photothermal therapy (PTT) and photodynamic therapy (PDT) effects. However, the hydrophobicity, instability, and low tumor uptake of IR780 limit its clinical applications. Here, we have structurally modified IR780 with hydroxychloroquine, an autophagy inhibitor, to synthesize a novel compound H780. H780 and IVM can form H780-IVM nanoparticles (H-I NPs) via self-assembly. Using hyaluronic acid (HA) to modify the H-I NPs, a novel nano-delivery system HA/H780-IVM nanoparticles (HA/H-I NPs) was synthesized for chemotherapy-phototherapy of colorectal cancer (CRC). Under NIR laser irradiation, HA/H-I NPs effectively overcame the limitations of IR780 and IVM and exhibited potent cytotoxicity. In vitro and in vivo experiment results showed that HA/H-I NPs exhibited excellent anti-CRC effects. Therefore, our study provides a novel strategy for CRC treatment that could enhance chemo-phototherapy by modulating autophagy.

Effects of traditional Chinese mind-body exercises on older adults with cognitive impairment: A systematic review and meta-analysis.

Objective: To determine the effectiveness of traditional Chinese mind-body exercises in improving cognition, memory, and executive function in older adults with cognitive impairment. Data sources: Relevant English and Chinese language studies published until September 14th, 2022 were retrieved from PubMed, Web of Science, Cochrane Library, Embase, CINAHL, WAN FANG DATA, VIP Information, CNKI, and SinoMed databases. Review methods: Randomized controlled trials assessing traditional Chinese mind-body exercises (Tai Chi, Baduanjin, Qigong, Mind-Body Therapies, and Yijinjing) in older adults with cognitive impairment were included. Two researchers independently identified eligible studies and extracted data. A risk-of-bias assessment was performed using the Cochrane Risk of Bias Tool. Results: This study included 15 randomized controlled trials (1,127 participants) from China, Thailand and American. Most studies had a high risk of bias in the blinding of participants and researchers, one study had a high risk of bias in the random sequence generation and two studies had a high risk of bias in the incomplete outcome data. Compared with conventional therapy alone, traditional Chinese mind-body exercises significantly improved global cognitive function (p < 0.00001), and Baduanjin could improve the global cognitive function (p < 0.00001), memory function (p < 0.0001), and executive function (p < 0.0001) outcomes after treatment, and significantly improved some dimensional scores on the auditory verbal learning test after treatment (p = 0.04). Conclusion: Compared with conventional therapy, traditional Chinese mind-body exercises (Tai Chi, Baduanjin, and Qigong) significantly improved global cognitive function, and Baduanjin could improve global cognitive function, memory function, and executive function in older adults with cognitive impairment. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, CRD42022327563.

Antioxidant Activity Evaluation of Oviductus Ranae Protein Hydrolyzed by Different Proteases.

As nutrition and a health tonic for both medicine and food, the protein content of Oviductus Ranae is more than 40%, making it an ideal source to produce antioxidant peptides. This work evaluated the effects of six different proteases (pepsin, trypsin, papain, flavourzyme, neutral protease and alcalase) on the antioxidant activity of Oviductus Ranae protein, and analyzed the relationship between the hydrolysis time, the degree of hydrolysis (DH) and the antioxidant activity of the enzymatic hydrolysates. The results showed that the antioxidant activity of Oviductus Ranae protein was significantly improved and the optimal hydrolysis time was maintained between 3-4 h under the action of different proteases. Among them, the protein hydrolysate which was hydrolyzed by pepsin for 180 min had the strongest comprehensive antioxidant activity and was most suitable for the production of antioxidant peptides. At this time, the DH, the DPPH radical scavenging activity, the absorbance value of reducing power determination and the hydroxyl radical scavenging activity corresponding to the enzymatic hydrolysate were 13.32 ± 0.24%, 70.63 ± 1.53%, 0.376 ± 0.009 and 31.96 ± 0.78%, respectively. Correlation analysis showed that there was a significant positive correlation between the hydrolysis time, the DH and the antioxidant activity of the enzymatic hydrolysates, further indicating that the hydrolysates of Oviductus Ranae protein had great antioxidant potential. The traditional anti-aging efficacy of Oviductus Ranae is closely related to the scavenging of reactive oxygen species, and its hydrolysates have better antioxidant capacity, which also provides support for further development of its traditional anti-aging efficacy.

Analysis of the Curative Effect of Alexandrite Laser in the Treatment of Venous Lake of Lips.

BACKGROUND AND OBJECTIVES: Laser is being widely used in clinical treatment nowadays, including 755 nm Alexandrite laser [1,2]. This study was conducted to examine the clinical outcome of long-pulse 755 nm Alexandrite laser in the treatment of venous lake of the lip. STUDY DESIGN/MATERIALS AND METHODS: Forty-one patients (2015-2019) were reviewed. The clinical outcomes were assessed 1 month after the treatment. The efficacy of the treatment was classified into four categories: basic recovery (most optimal outcome), effective, improvement, and ineffective (least favorable outcome). Adverse reactions were also recorded. RESULTS: Thirty-three (80.49%) patients achieved basic recovery and 8 (19.51%) were effective; 29 (70.73%) recovered after receiving one treatment, 3 (7.32%) recovered after receiving two treatments, and 1 (2.44%) recovered after three treatments. CONCLUSION: Long-pulse 755 nm Alexandrite laser is an effective treatment for the venous lake of the lip. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Herbal decoction of Gastrodia, Uncaria, and Curcuma confers neuroprotection against cerebral ischemia in vitro and in vivo.

"Tianma" (Gastrodia) and "gouteng" (Uncaria) are both widely used to treat cerebral ischemia. At the same time, "ezhu" (Curcuma longa) or turmeric, is derived from the dried roots of C. longa. It is a polyphenol known for its anti-inflammatory effects and its promotion of blood vessel endothelial function. This study explored the neuroprotective effects of a water extract of "tianma", "gouteng", and "ezhu" against ischemic injury. Flow cytometry analysis showed that Gastrodia, Uncaria, and Curcuma reduced the proportion of apoptotic cells in CoCl2 induced B35 (P = 0.0027) and SH-SY5Y (P = 0.0006) cell sample relative to the respective control group. Western blot indicated that Gastrodia, Uncaria, and Curcuma upregulated the expression of Bcl-2 and inversely downregulated Bax and Caspase-3 (P < 0.001). The infarct volume observed in the Gastrodia, Uncaria, and Curcuma group was also decreased compared with the control group (P < 0.05). Immunofluorescence detection revealed a lower expression of Caspase-7 in the Gastrodia, Uncaria, and Curcuma group than in the control group, while expression was negligible in the sham group. Gastrodia, Uncaria, and Curcuma confer neuroprotective effects in CoCl2 induced B35/SH-SY5Y cells and a rat model of ischemia by way of its anti-apoptotic effects.

Antitussive and Anti-inflammatory Dual-active Agents Developed from Natural Product Lead Compound 1-Methylhydantoin.

Natural products play an important role in drug discovery. This work employed a natural product 1-methylhydantoin as the lead compound to develop novel dual-active drugs. 1-Methylhydantoin was isolated from Oviductus Ranae, which is a traditional Chinese medicine that has been used for tussive and inflammation treatment for a long time. An in silico study screened the more active 1-methylhydantoin derivatives. Antitussive assessment indicated that the newly synthesized agent had similar bioactivity with the natural product. An anti-inflammatory model used xylene induced ear edema model. At the same dosage (100 mg/Kg), the newly prepared agent had an inhibition rate 53.18% which was much higher than that of the lead compound (22.69%). The results might be ascribed to the cyclooxygenases-1 (COX-1) and cyclooxygenases-2 (COX-2) selectivity, and the fitness of the compound, and the binding pocket. The anti-particulate matter (PM 2.5) acute pneumonia was evaluated through an in vivo model constructed by nasal instillation with PM 2.5 suspension. The results of the above models suggested that this novel agent had remarkable antitussive, anti-inflammatory, and anti-PM 2.5 acute pneumonia activities.

Protein-Based Fingerprint Analysis for the Identification of Ranae Oviductus Using RP-HPLC.

This work demonstrated a method combining reversed-phase high-performance liquid chromatography (RP-HPLC) with chemometrics analysis to identify the authenticity of Ranae Oviductus. The fingerprint chromatograms of the Ranae Oviductus protein were established through an Agilent Zorbax 300SB-C8 column and diode array detection at 215 nm, using 0.085% TFA (v/v) in acetonitrile (A) and 0.1% TFA in ultrapure water (B) as mobile phase. The similarity was in the range of 0.779-0.980. The fingerprint chromatogram of Ranae Oviductus showed a significant difference with counterfeit products. Hierarchical clustering analysis (HCA) and principal component analysis (PCA) successfully identified Ranae Oviductus from the samples. These results indicated that the method established in this work was reliable.

Melatonin ameliorates endoplasmic reticulum stress in N2a neuroblastoma cell hypoxia-reoxygenation injury by activating the AMPK-Pak2 pathway.

Endoplasmic reticulum (ER) stress has been identified as a primary factor involved in brain ischemia-reperfusion injury progression. p21-activated kinase 2 (Pak2) is a novel ER function regulator. The aim of our study is to explore the influence of Pak2 on ER stress and determine whether melatonin attenuates ER stress-mediated cell death by modulating Pak2 expression in vitro using N2a cells. The results of our study demonstrated that hypoxia-reoxygenation (HR) injury repressed the levels of Pak2, an effect that was accompanied by activation of ER stress. In addition, decreased Pak2 was associated with oxidative stress, calcium overload, and caspase-12-mediated apoptosis activation in HR-treated N2a cells. Interestingly, melatonin treatment reversed the decreased Pak2 expression under HR stress. Knockdown of Pak2 abolished the protective effects of melatonin on ER stress, oxidative stress, and caspase-12-related N2a cells death. Additionally, we found that Pak2 was regulated by melatonin via the AMPK pathway; inhibition of AMPK prevented melatonin-mediated Pak2 upregulation, a result that was accompanied by an increase in N2a cell death. Altogether, these results identify the AMPK-Pak2 axis as a new signaling pathway responsible for ER stress and N2a cell viability under HR injury. Modulation of the AMPK-Pak2 cascade via supplementation of melatonin might be considered an effective approach to attenuate reperfusion-mediated N2a cell damage via repression of ER stress.

Isolation and identification of two steroid compounds from Oviductus Ranae.

In this study, cholest-5-en-3ß,7ß-diol and 3ß-hydroxy-cholest-5-en-7-one were isolated from Oviductus Ranae by column chromatographies on Sephadex LH-20, octadecylsilyl (ODS) and pre high-performance liquid chromatography (HPLC). Their structures were elucidated on the basis of chemical and spectral analyses, including electrospray ionisation-mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR). The above two compounds were obtained from Oviductus Ranae for the first time.