High Contrast Detection of Carotid Neothrombus with Strong Near-Infrared Absorption Selenium Nanosphere Enhanced Photoacoustic Imaging.

Background: Carotid artery thrombosis is the leading cause of stroke. Since there are no apparent symptoms in the early stages of carotid atherosclerosis onset, it causes a more significant clinical diagnosis. Photoacoustic (PA) imaging provides high contrast and good depth information, which has been used for the early detection and diagnosis of many diseases. Methods: We investigated thrombus formation by using 20% ferric chloride (FeCl3) in the carotid arteries of KM mice for the thrombosis model. The near-infrared selenium/polypyrrole (Se@PPy) nanomaterials are easy to synthesize and have excellent optical absorption in vivo, which can be used as PA contrast agents to obtain thrombosis information. Results: In vitro experiments showed that Se@PPy nanocomposites have fulfilling PA ability in the 700 nm to 900 nm wavelength range. In the carotid atherosclerosis model, maximum PA signal enhancement up to 3.44, 4.04, and 5.07 times was observed by injection of Se@PPy nanomaterials, which helped to diagnose the severity of carotid atherosclerosis. Conclusion: The superior PA signal of Se@PPy nanomaterials can identify the extent of atherosclerotic carotid lesions, demonstrating the feasibility of PA imaging technology in diagnosing carotid thrombosis lesion formation. This study demonstrates nanocomposites and PA techniques for imaging and diagnosing carotid thrombosis in vivo.

Dachengqi Decoction alleviates intestinal inflammation in ovalbumin-induced asthma by reducing group 2 innate lymphoid cells in a microbiota-dependent manner.

Background and aim: Dachengqi Decoction (DCQD) as a classic traditional Chinese medicine has been reported to be effective in treating asthma, but its mechanism remains unknown. This study aimed to reveal the mechanisms of DCQD on the intestinal complications of asthma mediated by group 2 innate lymphoid cells (ILC2) and intestinal microbiota. Experimental procedure: Ovalbumin (OVA) was used to construct asthmatic murine models. IgE, cytokines (e.g., IL-4, IL-5), fecal water content, colonic length, histopathologic appearance, and gut microbiota were evaluated in asthmatic mice treated with DCQD. Finally, we administered DCQD to antibiotic-treated asthmatic mice to measure the ILC2 in the small intestine and colon. Results and conclusion: DCQD decreased pulmonary IgE, IL-4, and IL-5 levels in asthmatic mice. The fecal water content, the colonic length weight loss, and the epithelial damage of jejunum, ileum, and colon of asthmatic mice were ameliorated by DCQD. Meanwhile, DCQD greatly improved intestinal dysbiosis by enriching Allobaculum, Romboutsia and Turicibacter in the whole intestine, and Lactobacillus gasseri only in the colon. However, DCQD caused less abundant Faecalibaculum and Lactobacillus vaginalis in the small intestine of asthmatic mice. A higher ILC2 proportion in different gut segments of asthmatic mice was reversed by DCQD. Finally, significant correlations appeared between DCQD-mediated specific bacteria and cytokines (e.g., IL-4, IL-5) or ILC2. These findings indicate that DCQD alleviated the concurrent intestinal inflammation in OVA-induced asthma by decreasing the excessive accumulation of intestinal ILC2 in a microbiota-dependent manner across different gut locations.

Effect of thermal hydrolyzed sludge filtrate as an external carbon source on biological nutrient removal performance of A2/O system.

Thermal hydrolyzed sludge filtrate (THSF) rich in biodegradable organics could be a promising external carbon source for biological nutrient removal (BNR). The use of THSF can effectively reduce wastewater treatment plants operating costs and recover bioresources and bioenergy from the waste activated sludge. In this study, the effect of THSF on the BNR process was investigated using a lab-scale anaerobic/anoxic/oxic (A2/O) system. Total nitrogen (TN) and total phosphorus (TP) removal efficiencies of 74.26 ± 3.36% and 92.20 ± 3.13% at a 0.3% dosing ratio were achieved, respectively. Moreover, 20.42% of the chemical oxygen demand (COD) contained in THSF contributed to denitrification, enhancing nitrogen removal efficiency from 55.30 to 74.26%. However, the effluent COD increased by approximately 36.80%, due to 18.39% of the COD contained in THSF discharged with effluent. In addition, the maximum denitrification rate was approximately 16.01 mg N g VSS-1 h-1, while the nitrification rate was not significantly affected by THSF. Nitrosomonas, a common chemoautotrophic nitrifier, was not detected after the introduction of THSF. The aerobic denitrifier Rubellimicrobium was stimulated, and its relative abundance increased from 0.16 to 3.03%. Moreover, the relative abundance of Dechloromonas was 3.93%, indicating that the denitrifying phosphorus removal process was enhanced. This study proposes an engineering application route of THSF, and the chemical phosphate removal pretreatment might be a means to suppress the phosphate recirculation.

Comparison of the efficacy of gossypol acetate enantiomers in rats with uterine leiomyoma.

Gossypol acetate (GA), as the product of racemic gossypol and acetic acid conjugated by hydrogen bond, is hydrolyzed into gossypol to exert its effect on treating uterine leiomyoma (UL), which has been listed in China. But hypokalemia and mild changes of liver function limit its clinical application. It had been reported that the biological activities of gossypol optical isomers were different. In this study, we aimed to clarify whether there were differences in the efficacy of gossypol enantiomers and whether a single gossypol optical isomer could alleviate adverse reactions in the treatment of UL. The results indicated that (-)-GA and (+)-GA had significant therapeutic effect on rats with UL. Interestingly, (-)-GA could better significantly ameliorate the pathological structure, inhibit the secretion of estrogen, and downregulate the expression of estrogen receptor-alpha (ER-α) and progesterone receptor (PR) than (+)-GA. Additionally, (-)-GA could better evidently decrease the symptoms of abnormally elevated inflammatory factors caused by UL. In contrast, (-)-GA and (+)-GA had certain effects on potassium ion concentration in serum, liver and kidney function, and the effects of (+)-GA on liver function were more obvious than (-)-GA. These findings will be of great significance to the drug development of gossypol optical isomers.

Role of curcumin in the treatment of acute kidney injury: research challenges and opportunities.

BACKGROUND: Acute kidney injury (AKI) is a common complication in clinical inpatients, and it continues a high morbidity and mortality rate despite many clinical treatment measures. AKI is triggered by infections, surgery, heavy metal exposure and drug side effects, but current chemical drugs often fall short of expectations for AKI treatment and have toxic side effects. Therefore, finding new interventions and treatments, especially of natural origin, is of remarkable clinical significance and application. The herbal monomer curcumin is a natural phenolic compound extracted from the plant Curcuma longa and showed various biological activities, including AKI. Furthermore, recent studies have shown that curcumin restores renal function by modulating the immune system and the release of inflammatory mediators, scavenging oxygen free radicals, reducing apoptosis and improving mitochondrial dynamics. However, curcumin has a low bioavailability, which limits its clinical application. For this reason, it is essential to investigate the therapeutic effects and molecular mechanisms of curcumin in AKI, as well as to improve its bioavailability for curcumin formulation development and clinical application. PURPOSE: This review summarizes the sources, pharmacokinetics, and limitations in the clinical application of curcumin and explores methods to optimize its bioavailability using nanotechnology. In particular, the therapeutic effects and molecular mechanisms of curcumin on AKI are highlighted to provide a theoretical basis for AKI treatment in clinical practices. METHODS: This review was specifically searched by means of a search of three databases (Web of Science, PubMed and Science Direct), till December 2021. Search terms were "Curcumin", "Acute kidney injury", "AKI", " Pharmacokinetics", "Mitochondria" and "Nano formulations". The retrieved data followed PRISMA criteria (preferred reporting items for systematic review) RESULTS: Studies have shown that curcumin responded to AKI-induced renal injury and restored renal tubular epithelial cell function by affecting multiple signaling pathways in AKI models induced by factors such as cisplatin, lipopolysaccharide, ischemia/reperfusion, gentamicin and potassium dichromate. Curcumin was able to affect NF-κB signaling pathway and reduce the expression of IL-1ß, IL-6, IL-8 and TNF-α, thus preventing renal inflammatory injury. In the prevention of renal tubular oxidative damage, curcumin reduced ROS production by activating the activity of Nrf2, HO-1 and PGC-1α. In addition, curcumin restored mitochondrial homeostasis by upregulating OPA1 and downregulating DRP1 expression, while reducing apoptosis by inhibiting the caspase-3 apoptotic pathway. In addition, due to the low bioavailability and poor absorption of curcumin in vivo, curcumin nanoformulations including nanoparticles, liposomes, and polymeric micelles are formulated to improve the bioavailability. CONCLUSION: This review provides new ideas for the use of curcumin in the prevention and treatment of AKI by modulating the molecular targets of several different cellular signaling pathways.

Multi-Modal Optical Imaging and Combined Phototherapy of Nasopharyngeal Carcinoma Based on a Nanoplatform.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck with a high incidence rate worldwide, especially in southern China. Phototheranostics in combination with nanoparticles is an integrated strategy for enabling simultaneous diagnosis, real-time monitoring, and administration of precision therapy for nasopharyngeal carcinoma (NPC). It has shown great potential in the field of cancer diagnosis and treatment owing to its unique noninvasive advantages. Many Chinese and international research teams have applied nano-targeted drugs to optical diagnosis and treatment technology to conduct multimodal imaging and collaborative treatment of NPC, which has become a hot research topic. In this review, we aimed to introduce the recent developments in phototheranostics of NPC based on a nanoplatform. This study aimed to elaborate on the applications of nanoplatform-based optical imaging strategies and treatment modalities, including fluorescence imaging, photoacoustic imaging, Raman spectroscopy imaging, photodynamic therapy, and photothermal therapy. This study is expected to provide a scientific basis for further research and development of NPC diagnosis and treatment.

Combined Photothermotherapy and Chemotherapy of Oral Squamous Cell Carcinoma Guided by Multifunctional Nanomaterials Enhanced Photoacoustic Tomography.

BACKGROUND: Squamous cell carcinoma of the head and neck is the sixth most common cancer worldwide, with 40% occurring in the oral cavity. Although the level of early diagnosis and treatment of OSCC has improved significantly, the five-year survival rate of advanced patients remains unsatisfactory. However, the main challenges before us are how to get an early and accurate diagnosis and how to formulate effective treatment. Nanoparticle-based chemo-photothermal therapy has proven to be a promising non-invasive approach to treating oral squamous cell carcinoma treatment. METHODS: In this study, we tried to design and synthesize multifunctional hyaluronic acid (HA) modified gold nanorods/mesoporous silica-based nanoparticles loaded with doxorubicin hydrochloride (DOX) for photoacoustic imaging (PAI) guided cooperative chemo-photothermal therapy. RESULTS: The resultant nanocomposite shows favorable biocompatibility, relatively low cytotoxicity, ideal drug loading capability and strong PAI signals. In addition, they showed an excellent photothermal conversion efficiency of 49.02% for photothermal therapy (PTT). Moreover, in vivo and in vitro experiments have shown that synergistic chemo-photothermal therapy has better therapeutic effects than chemotherapy alone or PTT (P < 0.05). After being injected into the CAL-27 tumor-bearing mice, the DOX-AuNRs@mSiO2-HA nanoparticles could accumulate rapidly at the tumor sites and achieve complete ablation of tumors when combined with near-infrared laser irradiation, without obvious side effects on normal tissues. CONCLUSION: Our research provides a solid demonstration of the potential of DOX-AuNRs@mSiO2-HA as a multifunctional platform in PAI-guided photothermal chemotherapy for oral squamous cell carcinoma.

Ellagic acid protects ovariectomy-induced bone loss in mice by inhibiting osteoclast differentiation and bone resorption.

Osteoporosis is a devastating disease that features reduced bone quantity and microstructure, which causes fragility fracture and increases mortality, especially in the aged population. Due to the long-term side-effects of current drugs for osteoporosis, it is of importance to find other safe and effective medications. Ellagic acid (EA) is a phenolic compound found in nut galls, plant extracts, and fruits, and exhibits antioxidant and antineoplastic effects. Here, we showed that EA attenuated the formation and function of osteoclast dose-dependently. The underlying mechanism was further discovered by western blot, immunofluorescence assay, and luciferase assay, which elucidated that EA suppressed osteoclastogenesis and bone resorption mainly through attenuating receptor activator of nuclear factor-κB (NF-κB) ligand-induced NF-κB activation and extracellular signal-regulated kinase signaling pathways, accompanied by decreased protein expression of nuclear factor of activated T-cells calcineurin-dependent 1 and c-Fos. Moreover, EA inhibits osteoclast marker genes expression including Dc-stamp, Ctsk, Atp6v0d2, and Acp5. Intriguingly, we also found that EA treatment could significantly protect ovariectomy-induced bone loss in vivo. Conclusively, this study suggested that EA might have the therapeutic potentiality for preventing or treating osteoporosis.

Therapeutic Potential and Outlook of Alternative Medicine for Osteoporosis.

Osteoporosis, a bone disease resulting in the loss of bone density and microstructure quality, is often associated with fragility fractures, and the latter imposes a great burden on the patient and society. Although there are several different treatments available for osteoporosis such as hormone replacement therapy, bisphosphonates, Denosumab, and parathyroid hormone, some concerns have been raised regarding the inherent side effects of their long term use. It would be of great relevance to search for alternative natural compounds, which could complementarily overcome the limitations of the currently available therapy. Herein, we review current literature on natural compounds that might have therapeutic values for osteoporosis. Search terms included bone resorption, bone density, osteoporosis, postmenopausal, osteoporosis or bone density conservation agents, and any of the terms related to traditional, herbal, natural therapy, natural health, diet, or phytoestrogens. All the compounds and herbs included in the review are naturally bioactive or are used in folk herbal medicine and have been reported to be capable of attenuating osteopenia or osteoporosis in vivo or in vitro, through various mechanisms - estrogen-like activity, antioxidant and anti-inflammatory properties, or by modulating the key signaling pathways in the pathogenesis of osteoporosis. Through our assessment of the therapeutic potential and outlook of alternative medicine, we aim to provide an appealing perspective for the consideration of the application of a complementary anti-osteoporotic treatment option and prevention strategy for osteoporosis or osteolytic bone disorders.

[Chemical constituents from Rehmannia glutinosa].

OBJECTIVE: To study the chemical constituents from the roots of Rehmannia glutinosa. METHOD: The compounds were isolated by various chromatographic methods and identified by spectroscopic analysis. RESULT: Twelve compounds were isolated and their structures were identified as 5-hydroxymethyl-pyrrole-2-carbaldehyde (1), 5-hydroxymethyl furfural (2), tyrosol (3), 5,6-dihydroxy-beta-ionone (4), 6-O-E-feruloyl ajugol (5), acteoside (6), leucosceptoside A (7), martynoside (8), isomartynoside (9), purpureaside C (10), jionoside A1 (11), and jionoside B1 (12). CONCLUSION: Compounds 1, 3 and 9 were isolated from the genus Rehmannia for the first time.