DHA-enriched phosphatidylserine ameliorates high-fat diet-induced kidney injury in mice possibly by regulating TLR4/NF-κB and AMPK pathways.

The present study sought to investigate the amelioration effects of enzymatically synthesized docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on the high-fat diet (HFD)-induced kidney injury in mice. After 6 weeks of DHA-PS intervention, the mice's body weight in the 20 and 40 mg/kg DHA-PS groups decreased by 7.09% and 9.71%, respectively, compared to the HFD group. Especially, compared to the HFD group, 40 mg/kg DHA-PS treatment effectively reduced the levels of serum urea nitrogen by 68.48%, creatinine by 38.98%, kidney lipid accumulation (total cholesterol, triglycerides, and nonesterified fatty acids levels by 26.19%, 51.00%, and 26.11%), kidney or serum proinflammatory cytokines and enhanced the levels of kidney or serum oxidative stress parameters, except for malondialdehyde (MDA). Moreover, 40 mg/kg DHA-PS treatment decreased the expression levels of toll-like receptor 4 (TLR4) by 18.63%, IKKα by 31.81%, and p-p65 by 40.73% in the nuclear factor kappa-B pathway, thereby upregulating the expression levels of p-AMPKα by 64.93%, HSL by 99.60%, ATGL by 344.50%, PPARα by 162.02%, CPT1 by 167.95%, p-ACC1 by 144.92%, and p-SREBP1 by 1172.95%, and downregulating the expression levels of SREBP1 by 38.80%, ACC1 by 18.10%, and FAS by 82.28% in the AMPK pathway. Furthermore, our results also suggested that improving serum or kidney parameters and regulating intestinal microbial could affect each other after DHA-PS treatment. These results elucidated that DHA-PS could be a potential dietary supplement to alleviate HFD-induced kidney injury. PRACTICAL APPLICATION: Our results elucidated that DHA-PS could be a potential dietary supplement to alleviate HFD-induced kidney injury.

Monkfish Peptides Mitigate High Fat Diet-Induced Hepatic Steatosis in Mice.

Non-alcoholic fatty liver disease (NAFLD) is a hepatic metabolic syndrome usually accompanied by fatty degeneration and functional impairment. The aim of the study was to determine whether monkfish peptides (LPs) could ameliorate high-fat diet (HFD)-induced NAFLD and its underlying mechanisms. NAFLD was induced in mice by giving them an HFD for eight weeks, after which LPs were administered in various dosages. In comparison to the HFD control group: body weight in the LP-treated groups decreased by 23-28%; triacylglycerol levels in the blood decreased by 16-35%; and low-density lipoproteins levels in the blood decreased by 23-51%. Additionally, we found that LPs elevated the activity of hepatic antioxidant enzymes and reduced the inflammatory reactions within fatty liver tissue. Investigating the effect on metabolic pathways, we found that in LP-treated mice: the levels of phospho-AMP-activated protein kinase (p-AMPK), and phospho-acetyl CoA carboxylase (p-ACC) in the AMP-activated protein kinase (AMPK) pathway were up-regulated and the levels of downstream sterol regulatory element-binding transcription factor 1 (SREBP-1) were down-regulated; lipid oxidation increased and free fatty acid (FFA) accumulation decreased (revealed by the increased carnitine palmitoyltransferase-1 (CPT-1) and the decreased fatty acid synthase (FASN) expression, respectively); the nuclear factor erythroid-2-related factor 2 (Nrf2) antioxidant pathway was activated; and the levels of heme oxygenase-1 (HO-1) and nicotinamide quinone oxidoreductase 1 (NQO1) were increased. Overall, all these findings demonstrated that LPs can improve the antioxidant capacity of liver to alleviate NAFLD progression mainly through modulating the AMPK and Nrf2 pathways, and thus it could be considered as an effective candidate in the treatment of human NAFLD.

The Therapeutic Effect and the Possible Mechanism of C-Phycocyanin in Lipopolysaccharide and Seawater-Induced Acute Lung Injury.

Background: Seawater drowning-induced acute lung injury (ALI) is a severe clinical condition characterized by increased alveolar-capillary permeability, excessive inflammatory response, and refractory hypoxemia. C-phycocyanin (C-PC), a biliprotein found in blue-green algae such as spirulina platensis, is widely used in the food and dietary nutritional supplement fields due to its beneficial pharmacological effects. Previous studies have revealed that C-PC has anti-inflammatory, antioxidant, and anti-apoptotic activities. Purpose: Therefore, this study investigated the protective effect and underlying mechanisms of C-PC on lipopolysaccharide (LPS) and seawater (SW) induced ALI (SW and LPS-induced ALI). Methods: An SW and LPS mouse model of ALI mice was established through intratracheal administration of 5mg/kg LPS and 25% SW. Different doses of C-PC (100, 200 and 400 mg/kg) were administered by intraperitoneal injection for seven days. In addition, gap junction communication in RAW264.7 and MLE-12 cells was determined following stimulation with 25% SW and 10 µg/ml LPS after treatment with C-PC (120 µg/ml). Moreover, the arterial partial pressure of oxygen, lung wet/dry weight ratios, total protein content and MPO levels in the bronchoalveolar lavage fluid (BALF), and the histopathologic and ultrastructure staining of the lung tissues were determined. The oxidative stress index, levels of the pro-inflammatory mediators, epithelial cell viability and apoptosis, and the regulatory effect of C-PC on the NF-κB/NLRP3 axis were investigated. Results: The results showed that C-PC significantly alleviated pathological damages, suppressed oxidative stress, inflammation and apoptosis, and enhanced the viability of epithelial cells in the lung tissues. Furthermore, C-PC was shown to inhibit activation of the NF-κB/NLRP3 pathway and the formation of the NLRP3 inflammasome complex. Conclusions: In conclusion, C-PC shows promising therapeutic value in SW and LPS-induced ALI/ARDS, providing new insight into ALI/ARDS treatment.

Circ_0058063 promotes progression of thyroid cancer by sponging miR-330-3p/SDC4 axis.

Circular RNA takes a crucial part in carcinogenesis. Circ_0058063 has been found to act as an oncogene in esophageal cancer and bladder cancer, but its role in thyroid cancer (TC) is still under investigation. Therefore, we carried out a study to understand its role in TC and its association with miR-330-3p. The circ_0058063 and miR-330-3p in TC tissues and cells were quantified by quantitative reverse transcription PCR, and cell counting kit-8 and scratch adhesion test were conducted for evaluation of cell proliferation and migration. In addition, a dual luciferase reporter assay and RNA immunoprecipitation assay were conducted for interaction analysis between circ_0058063 and miR-330-3p. Circ_0058063 was upregulated in TC tissues and cells, but miR-330-3p expression showed an opposite trend. Both silencing circ_0058063 and upregulating miR-330-3p can suppress the proliferation and migration of TC cells, upregulate Bax, and downregulate Bcl-2. In addition, circ_0058063 is able to target miR-330-3p that is also able to target syndecan 4 (SDC4). circ_0058063 can act as a carcinogen in cases with TC via the miR-330-3p/SDC4 axis.

Engineered Exosomes: A Promising Drug Delivery Strategy for Brain Diseases.

Exosomes are a heterogeneous group of nano-sized natural membrane vesicles released from various cells and exist in body fluids. Different from the previous understanding of the function of exosomes as "garbage bins", exosomes act as carriers with many kinds of bioactive molecules (e.g., proteins, lipids, and nucleic acids) to play an important role in cell-cell communication. Growing evidence in recent years has suggested that exosomes also play some roles in the pathogenesis, diagnosis, and treatment modalities of some brain diseases, including ischemic stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and brain cancers. Exosomes as therapeutic drug carriers for brain drug delivery have received extensive attention as well as exosomes can overcome the blood-brain barrier (BBB). However, the low targeting ability and size-dependent cellular uptake of native exosomes could profoundly affect the delivery performance of exosomes. Recent studies have indicated that engineered exosomes can increase the drug uptake efficiency and the subsequent drug efficacy. In the present paper, we will briefly introduce the engineering methods and applications of engineered exosomes in the treatment of brain diseases, and then focus on discussing the advantages and challenges of exosome- based drug delivery platforms to further enrich and boost the development of exosomes as a promising drug delivery strategy for brain diseases.

Triplex-forming oligonucleotides as an anti-gene technique for cancer therapy.

Triplex-forming oligonucleotides (TFOs) can bind to the major groove of double-stranded DNA with high specificity and affinity and inhibit gene expression. Triplex-forming oligonucleotides have gained prominence because of their potential applications in antigene therapy. In particular, the target specificity of triplex-forming oligonucleotides combined with their ability to suppress oncogene expression has driven their development as anti-cancer agents. So far, triplex-forming oligonucleotides have not been used for clinical treatment and seem to be gradually snubbed in recent years. But triplex-forming oligonucleotides still represent an approach to down-regulate the expression of the target gene and a carrier of active substances. Therefore, in the present review, we will introduce the characteristics of triplex-forming oligonucleotides and their anti-cancer research progress. Then, we will discuss the challenges in their application.

[Controlled study on treatment of cervical spondylopathy of the nerve root type with acupuncture, moxibustion and massage as main].

OBJECTIVE: To probe into clinical value of comprehensive program of acupuncture, moxibustion and massage as main for treatment of cervical spondylopathy of the nerve root type. METHODS: Five centers, single blind, randomized controlled method were used, 660 cases were divided into a treatment group of 317 cases and a control group of 311 cases. They were treated respectively with comprehensive program of acupuncture, moxibustion and massage as main, and comprehensive program of physical therapy as main. Establish syndrome detection scale and multiply dimensional effect assessment indexes, and evaluate the therapeutic effects and safety. RESULTS: The cured rate, the cured-markedly effective rate were 42.9%, 64.4% in the treatment group, respectively, better than 16.7%, 36.3% in the control group (P<0.01); after treatment of 2 weeks, clinical symptoms improved in the both groups, but the treatment group was better than the control group in the improvement degrees of neck-shoulder-limb pain, neck rigidity, abnormality of cervical anteflexion, etc. (P<0.01 or P<0.05); the treatment group was shorter than the control group in the time of producing the effect and therapeutic course (P<0.01). CONCLUSION: Comprehensive program of acupuncture, moxibustion and massage as main is safe and effective for treatment of cervical spondylopathy, with a better therapeutic effect compared with the comprehensive program of physical therapy.

[Observation on therapeutic effect of warming needle moxibustion on knee osteoarthritis of deficiency-cold type].

OBJECTIVE: To compare clinically therapeutic effects of warming needle moxibustion and simple acupuncture on knee osteoarthritis. METHODS: One hundred and twenty cases conformed with the diagnostic criteria of knee osteoarthritis with TCM kidney-yang deficiency and cold syndrome were randomly divided into a warming needle moxibustion group and a simple acupuncture group. Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36) and others were selected in the two groups. Their therapeutic effects were assessed with joint pain scale, knee osteoarthritis severity index scale and cold syndrome differentiation factors. RESULTS: Both warming needle moxibustion and simple acupuncture could alleviate pain of knee osteoarthritis, improve dysfunction of the knee joint, reduce symptoms. The clinically basic cured rate and the total effective rate were 32.1% and 96.4% in the warming needle moxibustion group, which were better than 7.4% and 92.6% in the simple acupuncture group. CONCLUSION: Warming needle moxibustion is an effective therapy for knee osteoarthritis with kidney-yang deficiency and cold type.

[Clinical study on combination of acupuncture, cupping and medicine for treatment of fibromyalgia syndrome].

OBJECTIVE: To observe the therapeutic effect of acupuncture at five mental points and moving cupping on the Hechelu of the back on fibromyalgia syndrome (FS). METHODS: Sixty-six cases who conformed to the criteria were randomly divided into the treatment group treated with acupuncture at five mental points, moving cupping on the Hechelu of the back and amitriptyline, and the control group treated with amitriptyline. Clinical therapeutic effects were assessed with McGill Pain Questionnaire (MPQ) and HAMD depression scale. RESULTS: The therapeutic effect of the treatment group was better than that of the control group with a significant difference between the two groups (P < 0.01). CONCLUSION: Combination of acupuncture with cupping therapy is an effective therapy for fibromyalgia syndrome.

[Clinical observation on moving cupping therapy combined with moxibustion for treatment of senile habitual constipation].

OBJECTIVE: To explore an effective method for treatment of senile habitual constipation. METHODS: Sixty-four cases were randomly divided into a treatment group treated with moving cupping at Hechelu plus Shenque (CV 8) Bazhenxue moxibustion, and a control group with oral administration of Tab phenolphthaleinum, 32 cases in each group. Improvement of constipation in the patients were observed and compared. RESULTS: The short-term (14 days) clinical cured-markedly effective rate was 84.4% in the treatment group, which was significantly better than 59.4% of the control group (P < 0.05), and there was a significant difference between the two groups in the long-term (2 months) therapeutic effect (P < 0. 01). CONCLUSION: Moving cupping at the Hechelu combined with Shenque (CV 8) Bazhenxue moxibustion is an effective method for senile habitual constipation.