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.

Evidence and potential mechanisms of traditional Chinese medicine for the treatment of psoriasis vulgaris: a systematic review and meta-analysis.

Psoriasis vulgaris (PV) not only affects patients' skin health but also increases the risk of coronary heart disease and diabetes, which brings both physical and mental harms. Its pathogenesis is complex, and the multitarget effect of traditional Chinese medicine (TCM) is especially advantageous. Because a considerable number of randomized controlled trials related to TCM exhibit design defects, small sample size, or inadequate intervention time, so the status of TCM in the treatment of PV cannot be fully clarified. We reviewed the controlled clinical trials published over the past decade and selected 17 high-quality articles from over 2000 papers. The results suggest that TCM might be beneficial for decrease in PASI scores, thus, TCM might be an effective alternative therapy for PV management. The safety of TCM on PV was also assessed in our analysis. The more strictly designed and long-term observations of TCM for PV are supposed to be conducted in the future.

A prospective cohort study of cord blood 25(OH)D3 and food allergies in 6-month-old Chinese infants.

BACKGROUND: Vitamin D is closely related to childhood allergic diseases, such as food allergies, atopic dermatitis, and asthma. However, it is unclear whether vitamin D status in the cord blood from mothers is related to food allergies in infants. OBJECTIVE: We performed a prospective cohort study on the relationship between the cord blood vitamin D [i.e., 25-hydroxyvitamin D3(25(OH)D3)] level and infant food allergies. METHODS: This study selected 741 newborns to observe until 6 months of age and used open oral food challenges (OFCs) to diagnose their food allergies. Cord blood and 6-month serum 25(OH)D3 levels of the infants were measured by liquid chromatography-tandem mass spectrometry. RESULTS: The proportion of children with cord blood 25(OH)D3 deficiency (< 20 ng/mL) was 86.27%. Cord blood vitamin D was positively correlated with the supplementation frequency of egg yolk, multivitamins, calcium, and docosahexaenoic acid (DHA) during pregnancy and the mother's age. No significant difference was found in the cord blood 25(OH)D3 level between summer born and winter born infants (p = 0.465). After adjusting for seasonal factors, the risk of food allergies in the 25(OH)D3 non-deficiency group was 2.72 times that of the 25(OH)D3 deficiency group. Infants in the 25(OH)D3 non-deficiency group ≥20 ng/mL) had a higher risk of allergies compared with the deficiency group (< 20 ng/mL) (RR = 2.49). CONCLUSIONS: Cord blood 25(OH)D3 is associated with infant food allergies. Maintaining 25(OH)D3 in maternal cord blood at a low level may be conducive to the prevention of infant food allergies.

Engineering a self-navigated MnARK nanovaccine for inducing potent protective immunity against novel coronavirus.

Effective vaccines are vital to fight against the COVID-19 global pandemic. As a critical component of a subunit vaccine, the adjuvant is responsible for strengthening the antigen-induced immune responses. Here, we present a new nanovaccine that comprising the Receptor-Binding Domain (RBD) of spike protein and the manganese nanoadjuvant (MnARK), which induces humoral and cellular responses. Notably, even at a 5-fold lower antigen dose and with fewer injections, the MnARK vaccine immunized mice showed stronger neutralizing abilities against the infection of the pseudovirus (~270-fold) and live coronavirus (>8-fold) in vitro than that of Alum-adsorbed RBD vaccine (Alu-RBD). Furthermore, we found that the effective co-delivery of RBD antigen and MnARK to lymph nodes (LNs) elicited an increased cellular internalization and the activation of immune cells, including DCs, CD4+ and CD8+ T lymphocytes. Our findings highlight the importance of MnARK adjuvant in the design of novel coronavirus vaccines and provide a rationale strategy to design protective vaccines through promoting cellular internalization and the activation of immune-related pathways.

The effect of Ganodermalucidum spore oil in early skin wound healing: interactions of skin microbiota and inflammation.

The mushroom Ganoderma lucidum (G. lucidum Leyss. ex Fr.) Karst has been a traditional Chinese medicine for millennia. In this study, we isolated the Ganoderma lucidum spore oil (GLSO) and evaluated the effect of GLSO on skin burn wound healing and the underlying mechanisms. Mice were used to perform skin wound healing assay. Wound analysis was performed by photography, hematoxylin/eosin staining, Masson's Trichrome staining and immunohistochemical analysis. Microbiota on the wounds were analyzed using the 16s rRNA sequence and quantitative statistics. The lipopolysaccharide (LPS) content was examined in skin wounds and serum using an enzyme-linked immunosorbent assay (ELISA). The expression of Toll-like receptor 4 (TLR4) and the relative levels of inflammatory cytokines were determined by qPCR and immunofluorescence assay. A pseudo-germfree mouse model treated with antibiotics was used to investigate whether GLSO accelerated skin burn wound healing through the skin microbiota. We found that GLSO significantly accelerated the process of skin wound healing and regulated the levels of gram-negative and gram-positive bacteria. Furthermore, GLSO reduced LPS and TLR4, and levels of some other related inflammatory cytokines. The assay with the pseudo-germfree mice model showed that GLSO had a significant acceleration on skin wound healing in comparison with antibiotic treatment. Thus, GLSO downregulated the inflammation by regulating skin microbiota to accelerate skin wound healing. These findings provide a scientific rationale for the potential therapeutic use of GLSO in skin burn injury.

Ganoderma lucidum spore oil induces apoptosis of breast cancer cells in vitro and in vivo by activating caspase-3 and caspase-9.

ETHNOPHARMACOLOGICAL RELEVANCE: The mushroom Ganoderma lucidum (G. lucidum) is a traditional Chinese medicine reported to have a variety of pharmacological properties, including anti-cancer activity. G. lucidum spore oil (GLSO) is a lipid substance extracted from sporoderm-broken spore of G. lucidum. However, the effect of GLSO on breast cancer and the underlying molecular mechanism remain unclear. AIM OF THE STUDY: The aim of this study was to identify the effects of GLSO on breast cancer cells in vitro and in vivo as well as to investigate the mechanistic basis for the anticancer effect of GLSO. MATERIALS AND METHODS: First, in vitro MDA-MB-231 cells were treated with GLSO (0.2, 0.4, and 0.6 µL/mL). The protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), X-linked inhibitor of apoptosis (XIAP), total poly (ADP-ribose) polymerase (PARP), caspase-3 and caspase-8 were examined using western blotting. The mRNA expression levels of Fas-associated protein with death domain (FADD), TNF receptor-associated factor 2 (TRAF2), caspases-3, -8, -9 and Bax were examined using qRT-PCR. Second, in vivo the anticancer properties of GLSO were assessed by H&E, TUNEL and immunohistochemistry in BALB/c mice injected with 4T1 cells. In addition, the levels of caspase-9/caspase-3 signaling pathway proteins in tumor tissue were evaluated by immunoblotting. Finally, MDA-MB-231 cells were treated with caspase inhibitors to measure cell viability, the protein levels were examined with western blotting. RESULTS: The results in vitro showed that GLSO up-regulated the expression of Bax and caspase-3 in MDA-MB-231 cells, but had no effect on the expression of caspase-8. Moreover, the growth of tumors in vivo was significantly suppressed in the GLSO-treated group. The results of Western blot were consistent with in vitro. In vitro, co-treatment of MDA-MB-231 cells with caspase inhibitors reduced the inhibitory effect of GLSO on cell growth. CONCLUSIONS: GLSO inhibits the growth of MDA-MB-231 cells and tumors in vivo by inducing apoptosis, which may be achieved through the mitochondrial apoptotic pathway.

Probiotics supplementation in children with asthma: A systematic review and meta-analysis.

AIM: To systematically review the effects of probiotics supplementation in children with asthma. METHODS: An electronic search was conducted on PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure Database, CQ VIP Database and Wanfang Data until November 2017. The reference lists of included studies and pertinent reviews were checked for supplementing our search. Randomised control trials that compared probiotics versus placebo were included. RESULTS: Eleven studies with a total of 910 children met eligibility criteria. The pooled data revealed that the proportion of children with fewer episodes of asthma was significantly higher in the probiotics group than in the control group (risk ratio 1.3, 95% confidence interval (CI) 1.06-1.59); the reduction of IL-4 (mean differences -2.34, 95% CI -3.38, -1.29) and the increasing of interferon-γ (mean differences 2.5, 95% CI 1.23-3.76) was also significant after the treatment of probiotics. Nevertheless, no statistical significance was observed in childhood asthma control test, asthmatic symptom in the day and night, the number of symptom-free days, forced expiratory volume in the first second predicted and peak expiratory flow. CONCLUSIONS: This systematic review does not confirm or rule out the beneficial effects of probiotics supplementation in children with asthma. More well-designed randomised control trials with larger sample sizes need to be conducted to evaluate the effects of probiotics in children with asthma in the future.

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

Hyperthermia worsens ischaemic brain injury through destruction of microvessels in an embolic model in rats.

PURPOSE: Basal lamina is a major part of the microvascular wall and plays a critical role in the integrity of microvasculature. The aim of this study is to determine whether hyperthermia worsens the destruction of microvascular integrity in the ischaemic injured brain. MATERIALS AND METHODS: Focal cerebral ischaemia was induced by embolising a pre-formed clot into the middle cerebral artery (MCA). Rats received either normothermic or hyperthermic treatment. Neurological score and infarct size were evaluated at 24 h after the MCA occlusion. Microvascular collagen type IV and laminin were measured with fluorescence microscopy. The activities of matrix metalloproteinases (MMP-2 and MMP-9) and plasminogen activators (tPA and uPA) were determined by zymography. RESULTS: Treatment with hyperthermia significantly increased infarct volume (p<0.01), cortex swelling (p<0.01), striatum swelling (p<0.05) and neurologic score (p<0.01) at 24 h after the MCA occlusion. Compared to the normothermic groups, hyperthermia significantly worsened the losses of microvascular basal lamina structure proteins, collagen type IV and laminin, at 6 h (p<0.001) and 24 h (p<0.01) after MCA occlusion. Hyperthermia increased the MMP-9 activity at 6 and 24 h after MCA occlusion compared with normothermia (p<0.05), whereas increased the MMP-2 activity at 6 h only (p<0.05). Hyperthermia also elevated uPA activity significantly at 6 and 24 h after MCA occlusion compared to normothermia (p<0.05). CONCLUSIONS: These results demonstrate that hyperthermia exacerbates the destruction of microvascular integrity possibly by increasing the activities of MMP-2, MMP-9 and uPA in the ischaemic cerebral tissues.

A safety study of a B-class CpG ODN in Sprague-Dawley rats.

Oligodeoxynucleotides containing CpG motifs (CpG ODNs) are potent immune activators and are being tested as anti-tumor, antimicrobial agents and as adjuvants in vaccines. Little has been reported, however, about the systematic and comprehensive safety evaluation on repeated CpG ODN administration. To investigate the safety profile of a newly developed CpG ODN, CpG 684, we conducted a 28-day repeated dose toxicity study in rats, at dose levels of 5, 20 and 150 µg CpG 684 per rat. No abnormalities in clinical observations, growth, urinalysis and bone marrow cell counts were found in CpG 684 treated rats. CpG 684 was proved biologically active, capable of up-regulating the expressions of CD40 and CD86 molecules. The monocyte numbers were increased at the dose levels of 20 and 150 µg per rat. The spleen weights were increased in female rats at the dose level of 150 µg per rat. Microscopically, 5, 20 and 150 µg per rat CpG 684 caused local inflammatory cell infiltration and hyperplasia of fibrous tissue at injection sites; the treatment of 5 and 150 µg per rat CpG 684 induced enhanced inflammatory reaction in inguinal lymphoid tissue, and the dose of 150 µg per rat induced cell hyperplasia in white pulp of spleen and white pulp expansion. CpG 684 at 150 µg per rat led to decreases in peripheral lymphocyte, serum globulin, glucose, alkaline phosphatase and K+ levels in female rats, and induced the decrease in serum albumin and total protein in rats of both sexes. The data from this study will provide an important reference for developing CpG 684 as an adjuvant for vaccines of human use.

A new 3,4-seco-lupane-type triterpenoid from the pulp of Acanthopanax senticosus (Rupr. et Maxim) Harms.

A new triterpenoid, 3,4-seco-lupane-20(29)-ene-3,28-dioic acid, together with three known lignans, (-)-schisandrin B, (-)-sesamin and (-)-syringaresinol, was isolated from the pulp of Acanthopanax senticosus (Rupr. et Maxim) Harms. Their structures were elucidated by means of physicochemical properties and spectroscopic methods (1D, 2D-NMR and MS).

[Effects of Liangxue Tongyu Formula on brain edema and expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rats with intracerebral hemorrhage].

OBJECTIVE: To investigate the effects of Liangxue Tongyu Formula (LXTYF), a compound traditional Chinese herbal medicine, on brain edema in rats with intracerebral hemorrhage and to explore the mechanism. METHODS: Intracerebral hemorrhage was induced by using the intrastriatal autologous blood injection. Rats were randomized into sham-operated (SO) group, intracerebral hemorrhage (ICH) group and LXTYF group. Rats in the LXTYF group were intragastrically administered with LXTYF every day while the other two groups were given normal saline. Brain water content was determined at 24, 48, 72, and 120 h after intracerebral hemorrhage. Matrix metalloproteinase-9 (MMP-9) level, and MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expressions in perihematoma area were detected by gelatin zymography and fluorescence quantitative real-time polymerase chain reaction at the four time points, respectively. RESULTS: Water content in the ICH group was highly elevated after intracerebral hemorrhage, and reached to the peak at 72 h. Compared with the ICH group, the LXTYF group had lower water contents at 48, 72 and 120 h after intracerebral hemorrhage (P<0.01). The difference in water content between the LXTYF and SO groups was significant only at 72 h (P<0.01). Although the pro-MMP-9 level and MMP-9 activity in the LXTYF and ICH groups were enhanced, they were still lower in the LXTYF group than in the ICH group (P<0.01 for 24, 48, 72 and 120 h, respectively). And there was no significant difference in them between the LXTYF group and the SO group at 120 h. Meanwhile, MMP-9 mRNA expressions were increased in the ICH and LXTYF groups, but the levels in the LXTYF group were significantly lower (P<0.01 for 48, 72 and 120 h, respectively) than those in the ICH group. Also, TIMP-1 mRNA expressions at 24, 48, 72 and 120 h after intracerebral hemorrhage were up-regulated in the LXTYF group, and there were significant differences in TIMP-1 expressions between the LXTYF group and ICH group after intracerebral hemorrhage (P<0.01). CONCLUSION: Liangxue Tongyu Formula ameliorates brain edema in rats after intracerebral hemorrhage by inhibiting MMP-9 expression and activity and up-regulating TIMP-1.

[Clinical research of Yiqi Sanju Formula in treating central obese men at high risk of metabolic syndrome].

OBJECTIVE: To observe the therapeutic effects of Yiqi Sanju Formula (YQSJF), a compound Chinese herbal medicine, on central obese men at high risk of metabolic syndrome (MS). METHODS: Compared with 30 healthy male volunteers, 45 central obese men were separated randomly into two groups and received the interventions with YQSJF and placebo respectively for 10 weeks. Baseline characteristics, insulin resistance, inflammation cytokines and plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) were evaluated before and after treatment. RESULTS: The score of homeostatic model assessment for insulin resistance (HOMA-IR) and the levels of C reactive protein (CRP), free fatty acid (FFA) and PAI-1 in obese men were higher than those in the control group, while t-PA was lower. After treatment, compared with placebo group, body mass index, waist, and waist-to-hip ratio were decreased significantly in subjects who received YQSJF (P<0.01). The score of HOMA-IR and the levels of CRP, FFA and PAI-1 were decreased significantly, and the level of t-PA was increased significantly (P<0.01). CONCLUSION: YQSJF can reduce obesity and insulin resistance in central obese men at high risk of MS and improve inflammation and fibrinolysis, which indicates that it can reduce the risk of atherosclerosis.

[Effects of Pollen Typhae total flavone on glucose and lipid metabolism in 3T3-L1 adipocytes].

OBJECTIVE: To observe the effects of Pollen Typhae total flavone (PTF) on glucose and lipid metabolism in 3T3-L1 adipocytes. METHODS: The content of glucose which disappeared from the culture medium after incubation with drugs for 24 hours was determined as glucose consumption of the cells. The activity of cells was detected by XTT method. The transport of glucose was observed by (3)H-glucose uptake method. The efflux of free fatty acid (FFA) from adipocytes was observed by the concentration of FFA in the culture medium. RESULTS: The glucose concentration in culture medium was significantly decreased with a concentration-dependent effect, when PTF concentrations were from 0.025 g/L to 0.4 g/L. The toxic effect on cells appeared while PTF concentration was 0.4 g/L, and the MTT value decreased. PTF also significantly increased glucose transportation in the 3T3-L1 adipocytes as rosiglitazone (ROS) did. At the same time, FFA concentration in culture medium was significantly decreased as compared to the normal control group, while ROS-treated group did not show any difference. CONCLUSION: PTF can increase insulin sensitivity by increasing glucose transportation and consumption in the 3T3-L1 adipocytes as well as decreasing the FFA efflux from the cells.