Fire acupuncture for plaque psoriasis case series.

OBJECTIVE: To investigate the clinical efficacy of fire acupuncture (FA) on plaque psoriasis (PP), exploring its suitable syndrome types, in order to achieve better therapeutic effects, accelerate the possibility of psoriasis skin lesion recovery, and provide assistance for clinical treatment. METHODS: A total of 8 patients with PP aged between 18 and 60 years were recruited and treated with FA once a week, and the lesion area and severity index (PASI), visual analog scale and pruritus were measured before, 2, 4 and 8 weeks after treatment and at the follow-up period (week 12), respectively. Visual analog scale, and dermoscopy were used for assessment. RESULTS: All patients showed improvement in pruritus after 1 FA treatment, and lesions were reduced to varying degrees after 2 weeks. Except for patients 5 and 8, who only achieved effective results due to severe disease, all other patients with psoriasis achieved significant results at 8 weeks after treatment. CONCLUSION: FA can significantly control the development of lesions, reduce the symptoms of PP lesions and pruritus, and help prevent psoriasis recurrence.

Protective effect of Tao Hong Si Wu Decoction against inflammatory injury caused by intestinal flora disorders in an ischemic stroke mouse model.

BACKGROUND AND AIMS: Recent studies have shown that intestinal flora are involved in the pathological process of ischemic stroke (IS). The potential protective effect of the traditional Chinese prescription, Tao Hong Si Wu Decoction (THSWD), against inflammatory injury after IS and its underlying mechanisms of action were investigated in the current study. METHODS: Fifty SPF(Specefic pathogen Free) male C57 mice were randomly assigned to sham operation, model, THSWD low-dose (6.5 g/kg), medium-dose (13 g/kg) and high-dose (26 g/kg) groups (10 mice per group). Mouse models of transient middle cerebral artery occlusion were prepared via thread embolism. Neurological function score, hematoxylin-eosin (HE) staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), 16S ribosomal DNA (rDNA) sequencing, quantitative reverse transcription PCR (qRT-PCR) and other methods were employed to elucidate the underlying molecular mechanisms. RESULTS: Notably, THSWD induced a reduction in the neurological function score (P < 0.01) and neuronal injury in brain tissue, increase in protein expression of Claudin-5 and zonula occludens-1 (ZO-1) in brain tissue(P < 0.01), and decrease in serum lipopolysaccharide (LPS)(P < 0.01), diamine oxidase (DAO)(P < 0.01) and D-lactic acid(P < 0.01, P < 0.05) levels to a significant extent. THSWD also inhibited the levels of tumor necrosis factor-α (TNF-α)(P < 0.01) and interleukin - 1ß (IL-1ß)(P < 0.01) in brain tissue, and increased alpha and beta diversity in ischemic stroke mice, along with a certain reversal effect on different microflora. Finally, THSWD inhibited the polarization of microglia cells(P < 0.01) and decreased the protein and gene expression of toll-like receptor-4 (TLR-4)(P < 0.01, P < 0.05) and nuclear factor kappa B (NF-κB)(P < 0.01) in brain tissue. CONCLUSION: Our data indicate that THSWD may interfere with inflammatory response in ischemic stroke by regulating intestinal flora and promoting intestinal barrier repair.

Robotic Actuation-Mediated Quantitative Mechanogenetics for Noninvasive and On-Demand Cancer Therapy.

Cell mechanotransduction signals are important targets for physical therapy. However, current physiotherapy heavily relies on ultrasound, which is generated by high-power equipment or amplified by auxiliary drugs, potentially causing undesired side effects. To address current limitations, a robotic actuation-mediated therapy is developed that utilizes gentle mechanical loads to activate mechanosensitive ion channels. The resulting calcium influx precisely regulated the expression of recombinant tumor suppressor protein and death-associated protein kinase, leading to programmed apoptosis of cancer cell line through caspase-dependent pathway. In stark contrast to traditional gene therapy, the complete elimination of early- and middle-stage tumors (volume ≤ 100 mm3) and significant growth inhibition of late-stage tumor (500 mm3) are realized in tumor-bearing mice by transfecting mechanogenetic circuits and treating daily with quantitative robotic actuation in a form of 5 min treatment over the course of 14 days. Thus, this massage-derived therapy represents a quantitative strategy for cancer treatment.

Genome-Wide Analysis of Aux/IAA Gene Family in Artemisia argyi: Identification, Phylogenetic Analysis, and Determination of Response to Various Phytohormones.

Artemisia argyi is a traditional herbal medicine plant, and its folium artemisia argyi is widely in demand due to moxibustion applications globally. The Auxin/indole-3-acetic acid (Aux/IAA, or IAA) gene family has critical roles in the primary auxin-response process, with extensive involvement in plant development and stresses, controlling various essential traits of plants. However, the systematic investigation of the Aux/IAA gene family in A. argyi remains limited. In this study, a total of 61 Aux/IAA genes were comprehensively identified and characterized. Gene structural analysis indicated that 46 Aux/IAA proteins contain the four typical domains, and 15 Aux/IAA proteins belong to non-canonical IAA proteins. Collinear prediction and phylogenetic relationship analyses suggested that Aux/IAA proteins were grouped into 13 distinct categories, and most Aux/IAA genes might experience gene loss during the tandem duplication process. Promoter cis-element investigation indicated that Aux/IAA promoters contain a variety of plant hormone response and stress response cis-elements. Protein interaction prediction analysis demonstrated that AaIAA26/29/7/34 proteins are possibly core members of the Aux/IAA family interaction. Expression analysis in roots and leaves via RNA-seq data indicated that the expression of some AaIAAs exhibited tissue-specific expression patterns, and some AaIAAs were involved in the regulation of salt and saline-alkali stresses. In addition, RT-qPCR results indicated that AaIAA genes have differential responses to auxin, with complex response patterns in response to other hormones, indicating that Aux/IAA may play a role in connecting auxin and other hormone signaling pathways. Overall, these findings shed more light on AaIAA genes and offer critical foundational knowledge toward the elucidation of their function during plant growth, stress response, and hormone networking of Aux/IAA family genes in A. argyi.

Association of coagulation markers with the severity of white matter hyperintensities in cerebral small vessel disease.

Background and purpose: This study aimed to explore the correlation and causal relationship between fibrinogen, D-dimer, and the severity of cerebral white matter hyperintensity (MMH). Methods: A retrospective analysis of 120 patients with cerebral small vessel disease (CSVD) confirmed by head MRI attending the Third Affiliated Hospital of Beijing University of Traditional Chinese Medicine from August 2021 to February 2023 was performed. According to the Fazekas scale score, the patients were divided into 42 cases in the mild group, 44 cases in the moderate group, and 34 cases in the severe group. The levels of fibrinogen and D-dimer were compared among the three groups; the correlations between fibrinogen, D-dimer, and WMH severity were further analyzed; and independent risk factors for WMH severity were explored using the multivariate ordered logistic regression analysis. Furthermore, a two-sample Mendelian randomization (MR) analysis was performed to investigate the genetically predicted effect of fibrinogen and D-dimer on WMH. Results: As the severity of WMH increased, the levels of D-dimer and fibrinogen also gradually increased, and the results showed a positive correlational association, with significant differences within the groups (all p < 0.05); the multivariate ordered logistic regression model showed that after adjusting for the relevant covariates, D-dimer (OR = 5.998, 95% CI 2.213-16.252, p < 0.001) and fibrinogen (OR = 9.074, 95% CI 4.054-20.311, p < 0.001) remained independent risk factors for the severity of WMH. In the MR study, the random-effect inverse variance weighted (IVW) model showed that increased levels of genetically predicted D-dimer (OR, 1.01; 95% confidence interval 0.95-1.06; p = 0.81) and fibrinogen (OR, 1.91; 95% confidence interval 0.97-3.78; p = 0.06) were not associated with increased risk of WMH. The authors did not obtain strong evidence of a direct causal relationship between D-dimer, fibrinogen, and WMH. Conclusion: In this retrospective-based study, the authors found possible associations between D-dimer, fibrinogen, and WMH, but there was no obvious causal evidence. Further efforts are still needed to investigate the pathophysiology between D-dimer, fibrinogen, and WMH.

Secondary analysis of newly diagnosed type 2 diabetes subgroups and treatment responses in the MARCH cohort.

OBJECTIVE: To incorporate new clusters in the MARCH (Metformin and AcaRbose in Chinese patients as the initial Hypoglycemic treatment) cohort of newly diagnosed type 2 diabetes (T2D) patients and compare the anti-glycemic effects of metformin and acarbose across different clusters. METHODS: K-means cluster analysis was performed based on six clinical indicators. The diabetic clusters in the MARCH cohort were retrospectively associated with the response to metformin and acarbose. RESULTS: A total of 590 newly diagnosed T2D patients were classified by data-driven clusters into the MARD (mild obesity-related diabetes) (34.1 %), MOD (mild obesity-related diabetes) (34.1 %), SIDD (severe insulin-deficient diabetes) (20.3 %) and SIRD (severe insulin-resistant diabetes) (11.5 %) subgroups at baseline. At 24 and 48 weeks, 346 participants had finished the follow-up. After the adjustment of age, gender, weight, baseline HbA1c, baseline fasting glucose and 2-h postprandial blood glucose (2hPG), metformin mainly decreased the fasting glucose (0.07 ± 0.89 vs -0.26 ± 0.83, P = 0.043) in the MARD subgroup presented with OGTT (oral glucose tolerance test) results compared with acarbose group at 24 weeks. Acarbose led to a greater decrease in 2hPG in the MOD subgroup compared with metformin group (0.08 ± 0.86 vs -0.24 ± 0.92, P = 0.037) at 24 weeks. There was a also significant interaction between cluster and treatment efficacy in HbA1c (glycated hemoglobin) reduction in metformin and acarbose groups at 24 and 48 weeks (pinteraction<0.001). CONCLUSIONS: Metformin and acarbose affected different metabolic variables depending on the diabetes subtype.

RNA-sequencing analysis reveals the co-biodegradation performance of crude oil by marine Chlorella vulgaris under norfloxacin stress.

In this study, the microalgal growth and crude oil (CRO) biodegradation by marine Chlorella vulgaris (C. vulgaris) were assessed under norfloxacin (NFX) stress. The presence of NFX negatively affected the bio-removal of CRO within 5 days, as the NFX concentration increased from 100 to 1600 µg/L, due to its toxicity as an antibiotic. However, its negative impact on the final degradation capabilities of C. vulgaris was less significant (P-value <0.05). After 9 days of cultivation, CRO bio-removal efficiencies still exceeded 90 %, while NFX bio-removal efficiencies maintained over 47 %. RNA-seq analysis revealed that the degradation of CRO and NFX was attributed to the combined action of functional genes involved in scavenging reactive oxygen species. The production of pigments and the bio-removal performance of C. vulgaris in CRO, NFX, and CRO & NFX coexistence media were consistent with the changes in the number of differentially expressed genes in these samples.

Loss of SARM1 ameliorates secondary thalamic neurodegeneration after cerebral infarction.

Ischemic stroke causes secondary neurodegeneration in the thalamus ipsilateral to the infarction site and impedes neurological recovery. Axonal degeneration of thalamocortical fibers and autophagy overactivation are involved in thalamic neurodegeneration after ischemic stroke. However, the molecular mechanisms underlying thalamic neurodegeneration remain unclear. Sterile /Armadillo/Toll-Interleukin receptor homology domain protein (SARM1) can induce Wallerian degeneration. Herein, we aimed to investigate the role of SARM1 in thalamic neurodegeneration and autophagy activation after photothrombotic infarction. Neurological deficits measured using modified neurological severity scores and adhesive-removal test were ameliorated in Sarm1-/- mice after photothrombotic infarction. Compared with wild-type mice, Sarm1-/- mice exhibited unaltered infarct volume; however, there were markedly reduced neuronal death and gliosis in the ipsilateral thalamus. In parallel, autophagy activation was attenuated in the thalamus of Sarm1-/- mice after cerebral infarction. Thalamic Sarm1 re-expression in Sarm1-/- mice increased thalamic neurodegeneration and promoted autophagy activation. Auotophagic inhibitor 3-methyladenine partially alleviated thalamic damage induced by SARM1. Moreover, autophagic initiation through rapamycin treatment aggravated post-stroke neuronal death and gliosis in Sarm1-/- mice. Taken together, SARM1 contributes to secondary thalamic neurodegeneration after cerebral infarction, at least partly through autophagy inhibition. SARM1 deficiency is a potential therapeutic strategy for secondary thalamic neurodegeneration and functional deficits after stroke.

Mechanism of analgesic effect of fire needle on peripheral sensitization in rats with neuropathic pain induced by chemotherapy. / ç«é’ˆå¯¹åŒ–ç–—æ‰€è‡´ç¥žç»ç— ç†æ€§ç–¼ç—›å¤§é¼ å¤–å‘¨æ•åŒ–çš„é•‡ç—›ä½œç”¨æœºåˆ¶.

OBJECTIVES: This study aims to explore the analgesic mechanism of fire needle on peripheral sensitization in rats with neuropathic pain(NP) induced by oxaliplatin, so as to investigate its mechanism in improving peri-pheral sensitization. METHODS: Male SD rats aged 8 weeks were randomly divided into 4 groups：normal group(n=6), model group(n=6), fire needle group(n=6), and medication group(n=6). NP rat model was established by intraperitoneal injection of oxaliplatin(4 mg/kg) on days 1, 2, 8, 9, 15, 16, 22, and 23. For rats in the fire needle group, fire needle treatment was performed at the "Jiaji"(EX-B2) acupoints of the L4-L6 segments on days 24, 26, and 28, ie. 1 day, 3 and 5 days after modeling. The medication group received intraperitoneal injection of pregabalin(100 mg/kg). Mechanical pain thresholds of the rats were measured before modeling, after modeling and intervention. Serum contents of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and chemokine ligand 12(CXCL12) were detected by ELISA. Skin histopathology changes in the acupoint area were observed using HE staining. The number of mast cells in the skin of the acupoints was observed using toluidine blue staining. Immunohistochemical staining was performed to detect the postive expressions of transient receptor potential vanilloid 1(TRPV1), protease-activated receptor 2(PAR2) and tryptase(TPS) in the skin of the acupoint area. Western blot was used to detect the protein expressions of TRPV1 and PAR2 in the dorsal root ganglia(DRG). RESULTS: Compared with the normal group, the model group had decreased paw withdrawal threshold(PWT) after modeling(P<0.05), increased serum contents of IL-6, TNF-α, and CXCL12(P<0.05), increased number of mast cells in the acupoint area(P<0.05), and increased positive protein expressions of TPS, TRPV1, and PAR2 in the skin of the acupoint area(P<0.05). Compared with the model group, the fire needle group and medication group had increased PWT after intervention(P<0.05), decreased serum contents of IL-6, TNF-α, and CXCL12, and postive protein expressions of TPS, TRPV1, and PAR2 in the skin of the acupoint area(P<0.05)；while the medication group had decreased protein expressions of TRPV1 and PAR2 in DRG(P<0.05). HE staining showed thickened epidermis, disordered cellular arrangement, significant intercellular edema, and inflammatory cell infiltration in the model group. In the medication and fire needle groups, the epidermis was thinner, cellular arrangement was clearer, and the extent of tissue edema and inflammatory cell infiltration was reduced compared to the model group. CONCLUSIONS: Fire needle can improve mechanical pain threshold and reduce the contents of peripheral inflammatory factors in rats with oxaliplatin-induced NP. This effect may be related to the inhibition of mast cell activation and the inhibition of TPS, TRPV1 and PAR2 protein expressions, in the local areas of acupoints.

A randomized, controlled clinical trial of acupoint catgut embedding as an effective control of functional anorectal pain.

BACKGROUND: Patients with functional anorectal pain (FAP) usually feel pain in the anal region, foreign body sensation, and defecation disorders. The pain may radiate to the perineum, thighs, and waist. Conventional biofeedback, local nerve block and surgical treatment have certain limitations. Thread-embedding acupuncture (TEA) is a complementary and alternative therapy, which is widely used in the clinical practice of traditional Chinese medicine to treat functional anorectal pain. This study evaluated the efficacy and safety of the catgut-embedding acupuncture in patients with FAP. METHODS: FAP patients were enrolled and randomly divided into a thread-embedding acupuncture group (n = 35) and a sham-embedding acupuncture control group (n = 36). Patients underwent treatment twice monthly for 2 months and were assessed before and after treatments for visual analogue scales (VAS) of anorectal pain, VAS of lumbar pain or soreness, VAS of abdominal distension or pain, anal incontinence index, and SF-36 quality of life. The SF-36 quality of life score included assessment of physical functioning, role-physical, bodily-pain, general health, role-emotional, social functioning, vitality, and mental health. RESULT: The total effective rate was 85.71% for the treatment group versus 8.33% of the controls after 2 months (P < .001). The patients' anal rectum VAS score was significantly higher after treatment versus pretreatment (P < .01), while the physical functioning, role-physical, bodily-pain, role-emotional, and mental health in the experimental group and the role-emotional, and mental health in the control group were all significantly improved versus pretreatment (P < .05). The anorectal VAS score, anal incontinence index, and the SF-36 scores of the physical functioning, role-physical, bodily-pain, role-emotional, and mental health were better in the treatment group compared to the control group (P < .05). Most importantly, there were no adverse reactions observed in either group during the treatment. CONCLUSION: The thread-embedding acupuncture treatment effectively and safely improved the emotional anxiety and quality of life in FAP patients.

Hederasaponin C inhibits LPS-induced acute kidney injury in mice by targeting TLR4 and regulating the PIP2/NF-κB/NLRP3 signaling pathway.

Acute kidney injury (AKI) is a common clinical condition associated with increased incidence and mortality rates. Hederasaponin C (HSC) is one of the main active components of Pulsatilla chinensis (Bunge) Regel. HSC possesses various pharmacological activities, including anti-inflammatory activity. However, the protective effect of HSC against lipopolysaccharide (LPS)-induced AKI in mice remains unclear. Therefore, we investigated the protective effect of HSC against LPS-induced renal inflammation and the underlying molecular mechanisms. Herein, using MTT and LDH assays to assess both cell viability and LDH activity; using dual staining techniques to identify different cell death patterns; conducting immunoblotting, QRT-PCR, and immunofluorescence analyses to evaluate levels of protein and mRNA expression; employing immunoblotting, molecular docking, SPR experiments, and CETSA to investigate the interaction between HSC and TLR4; and studying the anti-inflammatory effects of HSC in the LPS-induced AKI. The results indicate that HSC inhibits the expression of TLR4 and the activation of NF-κB and PIP2 signaling pathways, while simultaneously suppressing the activation of the NLRP3 inflammasome. In animal models, HSC ameliorated LPS-induced AKI and diminished inflammatory response and the level of renal injury markers. These findings suggest that HSC has potential as a therapeutic agent to mitigate sepsis-related AKI.

[Electroacupuncture at acupoints of yangming meridians for sarcopenia: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of electroacupuncture at acupoints of yangming meridians for sarcopenia. METHODS: A total of 60 patients with sarcopenia were randomized into an observation group and a control group, 30 cases in each group. In the control group, conventional nutrition intervention for sarcopenia was adopted. In the observation group, on the basis of the treatment in the control group, acupuncture was applied at bilateral Binao (LI 14), Quchi (LI 11), Zusanli (ST 36), Yanglingquan (GB 34), etc.,ipsilateral Quchi (LI 11) and Zusanli (ST 36) were connected to electroacupuncture, with discontinuous wave, 2 Hz in frequency, 1-10 mA in intensity, 2 times a week, with a interval of 3 days. A total of 12-week treatment was required in the two groups. Before and after treatment, the appendicular skeletal muscle mass index (ASMI), grip strength, 6 m-walking time, body fat percentage and body moisture percentage were observed in the two groups. RESULTS: Compared with those before treatment, after treatment, ASMI and grip strength were increased while 6 m-walking time was shortened in the two groups (P<0.05); body fat percentage was decreased while body moisture percentage was increased in the observation group (P<0.05). After treatment, in the observation group, ASMI, grip strength and body moisture percentage were increased (P<0.05), 6 m-walking time was shortened and body fat percentage was decreased (P<0.05) compared with those in the control group. CONCLUSION: Electroacupuncture at acupoints of yangming meridians can effectively improve the skeletal muscle mass, muscle function, body fat percentage and body moisture percentage in patients with sarcopenia, and make the distribution of muscle and fat more reasonable.

[Clinical efficacy of fire needling combined with cupping therapy on herpes zoster of acute stage and the effect on Th17/Treg cellular immune balance].

OBJECTIVE: To compare the clinical efficacy between the combined therapy of fire needling and cupping, and western medication on herpes zoster of acute stage, as well as the effects on Th17 and Treg cells and inflammatory factors, i.e. IL-10 and IL-17 in the peripheral blood. METHODS: Eighty patients with herpes zoster of acute stage were randomly divided into a combined therapy (fire needling plus cupping) group and a western medication group, 40 cases in each one. In the combined therapy group, the pricking and scattering techniques with fire needle were used at ashi points and Jiaji (EX-B 2) corresponding to the affected spinal segments; afterwards, cupping therapy was delivered. The combined treatment was given once daily. In the western medication group, valaciclovir hydrochloride tablet and vitamin B1 tablet were administered orally. The duration of treatment in each group was 10 days. Before each treatment from day 1 to day 10 and on day 11 , the score of symptoms and physical signs was observed in the two groups separately. Before each treatment from day 1 to day 10 and on day 11, 30, 60, the score of visual analogue scale (VAS) and skin lesion indexes were observed in the two groups. On day 60, the incidence of postherpetic neuralgia was recorded in the two groups. The levels of Th17 and Treg cells, Th17/Treg ratio in the peripheral blood, as well as serum levels of IL-10 and IL-17 were detected before and after treatment in the two groups. The clinical efficacy was compared between the two groups. RESULTS: From day 6 to day 10 during treatment and on day 11, the scores of symptoms and physical signs in the combined therapy group were lower than those of the western medication group (P<0.05, P<0.01). On day 3, day 6 to day 10 during treatment and day 11, day 30, VAS scores in the combined therapy group were lower than those of the western medication group (P<0.05, P<0.01). On day 60, the incidence of postherpetic neuralgia in the combined therapy group was lower compared with that in the western medication group (P<0.05). The blister arresting time and scabbing time in the combined therapy group were shorter than those of the western medication group (P<0.05). After treatment, the level of Th17, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 were all lower in comparison with those in the western medication group (P<0.05). The curative and remarkably effective rate was 82.5% (33/40) in the combined therapy group, higher than 62.5% (25/40) in the western medication group (P<0.05). CONCLUSION: The early application of fire needling combined with cupping therapy can effectively treat herpes zoster of acute stage, relieve pain, and reduce the incidence of postherpetic neuralgia, which may be related to reducing the levels of Th17 and Treg cells, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 so that the cellular immune balance is modulated.

Garcinone E suppresses breast cancer growth and metastasis by modulating tumor-associated macrophages polarization via STAT6 signaling.

Cancer metastasis remains the most common cause of death in breast cancer patients. Tumor-associated macrophages (TAMs) are a novel therapeutic target for the treatment of metastatic breast cancer. Despite the good anti-cancer activity of garcinone E (GE), there are no reports on its therapeutic effects on breast cancer metastasis. The objective of this study was to examine the anti-cancer effects of GE on metastatic breast cancer. RAW 264.7 and THP-1 cells were polarized to M2 macrophages by IL-4/IL-13 in vitro. A 4T1 mouse breast cancer model and the tail vein breast cancer metastasis model were used to explore the effect of GE on breast cancer growth and metastasis in vivo. In vitro studies showed that GE dose-dependently suppressed IL-4 + IL-13-induced expression of CD206 in both RAW 264.7 cells and differentiated THP-1 macrophages. However, GE did not affect the LPS + IFN-γ-induced polarization to the M1-like macrophages in vitro. GE inhibited the expression of the M2 macrophage specific genes in RAW 264.7 cells, and simultaneously impaired M2 macrophage-induced breast cancer cell proliferation and migration, and angiogenesis. In animal studies, GE significantly suppressed tumor growth, angiogenesis, and lung metastasis in 4T1 tumor-bearing mice, without causing toxicity. In both tumor and lung tissues, the proportion of M2-like TAMs was significantly decreased while the proportion of M1-like TAMs was markedly increased by GE treatment. Mechanistically, GE inhibited phosphorylation of STAT6 in vitro and in vivo. Our results demonstrate for the first time that GE suppresses breast cancer growth and pulmonary metastasis by modulating M2-like macrophage polarization through the STAT6 signaling pathway.

Study on the Intervention Mechanism of Cryptotanshinone on Human A2780 Ovarian Cancer Cell Line Using GC-MS-Based Cellular Metabolomics.

Cryptotanshinone (CT), an active component of the traditional Chinese medicine Salvia miltiorrhiza Bunge, exhibits a wide range of biological and pharmacological activities. Although the anticancer activity of CT is well known, the knowledge of its effect on the regulation of cancer cell metabolism is relatively new. The present study investigated the anticancer mechanism of CT in ovarian cancer with a focus on cancer metabolism. CCK8 assays, apoptosis assays, and cell cycle assays were conducted to reveal the growth-suppressive effect of CT on ovarian cancer A2780 cells. To explore the potential underlying mechanisms of CT, the changes in endogenous metabolites in A2780 cells before and after CT intervention were investigated using the gas chromatography-mass spectrometry (GC-MS) approach. A total of 28 important potential biomarkers underwent significant changes, mainly involving aminoacyl-tRNA biosynthesis, energy metabolism, and other pathways. Changes in the ATP and amino acid contents were verified with in vitro and in vivo experiments. Our results indicate that CT may exert an anti-ovarian cancer effect by inhibiting ATP production, promoting the protein catabolic process, and inhibiting protein synthesis, which may lead to cell cycle arrest and apoptosis.

Immunological gadolinium-doped mesoporous carbon nanoparticles for tumor-targeted MRI and photothermal-immune co-therapy.

Photothermal therapy (PTT) is an effective and well-documented approach to thermally ablate tumors. However, the side effect of distal metastasis and recurrence limit its further expansion. At the same time as PTT was developed, the employment of imaging to monitor the treatment of tumors also became meaningful. Herein, as a proof of concept, gadolinium-doped mesoporous carbon nanoparticles (Gd-MCNs) were prepared as nanocarriers, MRI contrast agents, and PTT agents by a one-step hard template method, which realized Gd doping and carbon filling simultaneously, while retaining enough pore space for drug loading. After loading the immune adjuvant, R837, and the coating of tumor extracellular vesicle, the obtained biomimetic nanoparticles (EV@Gd-MCNs-R837) not only allowed tumor MRI, but also inhibited the primary tumor and its metastasis with long-term immune memory in vivo. This study provides proof for the potential of Gd-MCNs-based biomimetic nanoparticles for targeted PTT/immune-enhanced synergistic theranostic of tumors.

High Performance and Multifunction Moisture-Driven Yin-Yang-Interface Actuators Derived from Polyacrylamide Hydrogel.

High actuation performance of a moisture actuator highly depends on the presence of a large property difference between the two layers, which may cause interfacial delamination. Improving interfacial adhesion strength while increasing the difference between the layers is a challenge. In this study, a moisture-driven tri-layer actuator with a Yin-Yang-interface (YYI) design is investigated in which a moisture-responsive polyacrylamide (PAM) hydrogel layer (Yang) is combined with a moisture-inert polyethylene terephthalate (PET) layer (Yin) using an interfacial poly(2-ethylhexyl acrylate) (PEA) adhesion layer. Fast and large reversible bending, oscillation, and programmable morphing motions in response to moisture are realized. The response time, bending curvature, and response speed normalized by thickness are among the best compared with those of previously reported moisture-driven actuators. The excellent actuation performance of the actuator has potential multifunctional applications in moisture-controlled switches, mechanical grippers, and crawling and jumping motions. The Yin-Yang-interface design proposed in this work provides a new design strategy for high-performance intelligent materials and devices.

Transcriptomics and metabolomics revealed the pulmonary protective mechanism of Xixin-Ganjiang Herb Pair for warming the lungs to dissolve phlegm in COPD rats.

Xixin-Ganjiang Herb Pair (XGHP), a classic combination treatment to warm the lungs and dissolve phlegm, is widely used in the treatment of various pulmonary diseases. Chronic obstructive pulmonary disease (COPD) refers to a group of chronic obstructive airway diseases that can seriously harm human health. However, the effective components, targets, and pathways that underlie XGHP in the treatment of COPD remain unclear. Therefore, this study initially identified the effective components of XGHP through the use of UPLC-MS/MS and pharmacologic methods of traditional Chinese medicine. Secondly, transcriptomic analysis of the lung tissues of rats revealed the pharmacodynamic transcripts of each group, and metabolomics analysis revealed the differential metabolites associated with XGHP treatment. Finally, molecular docking of effective components with transcriptome genes was performed and western blotting was performed in order to determine the expression of related proteins in rat lung tissue. Overall, 30 effective components of XGHP were identified, including L-asarinin, 6-gingerol, sesamin, kaempferol, and quercetin. Transcriptomic studies demonstrated that expression of 386 genes recovered after XGHP treatment, and that they were mainly enriched in the oxidative phosphorylation and AMPK signaling pathways. According to the metabolomics studies, expression of eight metabolites differed between the COPD and the XGHP groups. These metabolites were mainly involved the biosynthesis of unsaturated fatty acids. Finally, the transcriptomic and metabolomics data were integrated. FASN and SCD in AMPK signaling pathway were directly linked to certain metabolites, including linoleic acid, palmitic acid, and oleic acid. These results indicate that XGHP can inhibit pAMPK expression and negatively regulate FASN and SCD expression during treatment of COPD in order to enhance the biosynthesis of unsaturated fatty acids and maintain energy homeostasis.

Glycyrrhetinic acid suppresses breast cancer metastasis by inhibiting M2-like macrophage polarization via activating JNK1/2 signaling.

BACKGROUND: Breast cancer metastasis is leading cause of cancer death among women worldwide. Tumor-associated macrophages (TAMs) have been considered as potential targets for treating breast cancer metastasis because they promote tumor growth and development. Glycyrrhetinic acid (GA) is one of the most important phytochemicals of licorice which has shown promising anti-cancer efficacies in pre-clinical trials. However, the regulatory effect of GA on the polarization of TAMs remains elusive. PURPOSE: To investigate the role of GA in regulating the polarization of M2 macrophages and inhibiting breast cancer metastasis, and to further explore its underlying mechanisms of action. STUDY DESIGN: IL-4 / IL-13-treated RAW 264.7 and THP-1 cells were used as the M2-polarized macrophages in vitro. A 4T1 mouse breast cancer model and the tail vein breast cancer metastasis model were applied to study the effect of GA on breast cancer growth and metastasis in vivo. RESULTS: In vitro studies showed that GA significantly inhibited IL-4 / IL 13-induced M2-like polarization in RAW 264.7 and THP-1 macrophages without affecting M1-like polarization. GA strongly decreased the expression of M2 macrophage markers CD206 and Arg-1, and reduced the levels of the pro-angiogenic molecules VEGF, MMP9, MMP2 and IL-10 in M2 macrophages. GA also increased the phosphorylation of JNK1/2 in M2 macrophages. Moreover, GA significantly suppressed M2 macrophage-induced cell proliferation and migration in 4T1 cancer cells and HUVECs. Interestingly, the inhibitory effects of GA on M2 macrophages were abolished by a JNK inhibitor. Animal studies showed that GA significantly suppressed tumor growth, angiogenesis, and lung metastasis in BALB/c mice bearing breast tumor. In tumor tissues, GA reduced the number of M2 macrophages but elevated the proportion of M1 macrophages, accompanied by activation of JNK signaling. Similar results were found in the tail vein breast cancer metastasis model. CONCLUSION: This study demonstrated for the first time that GA could effectively suppress breast cancer growth and metastasis by inhibiting macrophage M2 polarization via activating JNK1/2 signaling. These findings indicate that GA could be served as the lead compound for the future development of anti-breast cancer drug.

Anti-Inflammatory and Anti-Osteoclastogenesis Activities of Different Kinds of Zanthoxylum bungeanum Seed Oil in Vitro.

Our previous study has exhibited that one kind of Zanthoxylum bungeanum seed oil (ZSO), extracted from Zanthoxylum bungeanum seed, had inhibitory effects on osteoclastogenesis. However, the anti-osteoclastogenesis activities of different kinds of ZSO are scarcely reported. Since inflammation is related to bone loss and osteoporosis, in this study, three kinds of ZSO, Zanthoxylum schinifolium Siebold et Zucc seed oil (ZSSO), Zanthoxylum armatum DC. seed oil (ZDSO) and Zanthoxylum bungeanum maximum seed oil (ZBSO), were obtained with Soxhlet extraction and their fatty acid constituents were detected by GC-FID. RAW264.7 macrophages induced by lipopolysaccharide (LPS) were used to evaluate the inhibitory effects of three kinds of ZSO on inflammation via detecting the expression levels of inflammatory factors by RT-qPCR. Moreover, RANKL-induced osteoclastogenesis was applied to demonstrate the anti-osteoclastogenesis activities of them through tartrate-resistant acid phosphatase (TRAP) staining and RT-qPCR. The GC-FID results exhibited that the highest constituent in ZSSO and ZDSO was oleic acid (OA) and palmitoleic acid (PLA), respectively. While linoleic acid (LA) and α-Linolenic acid (ALA) in ZBSO were dominant. At the concentration of 0.5 µL/mL, all three kinds of ZSO could decrease the expression levels of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß) in LPS-induced macrophages. At the concentration of 0.25 µL/mL, only ZSSO could decrease the expression levels of iNOS and COX-2, which implied the inhibitory effects of ZSSO were stronger than other ZSOs. The number of RANKL-induced osteoclasts and the expressions of nuclear factor kappa-B (NF-κB), TNF-α and IL-6 in the cells were decreased after being treated with ZSOs at the concentration of 0.5 µL/mL, while the number of RANKL-induced osteoclasts after treated with ZBSO were less than those treated with other ZSOs, this indicated that the anti-osteoclastogenesis effect of ZBSO were stronger than other ZSOs. In conclusion, the fatty acid compositions of three major kinds of ZSO were compared and the content of unsaturated fatty acids especially ω-3 polyunsaturated fatty acids in ZBSO were the highest among them. All ZSOs tested had anti-inflammatory and anti-osteoclastogenesis activities. And their anti-osteoclastogenesis effects might be related to the suppression of the NF-κB pathway.