Nomo1 deficiency causes autism-like behavior in zebrafish.

Patients with neuropsychiatric disorders often exhibit a combination of clinical symptoms such as autism, epilepsy, or schizophrenia, complicating diagnosis and development of therapeutic strategies. Functional studies of novel genes associated with co-morbidities can provide clues to understand the pathogenic mechanisms and interventions. NOMO1 is one of the candidate genes located at 16p13.11, a hotspot of neuropsychiatric diseases. Here, we generate nomo1-/- zebrafish to get further insight into the function of NOMO1. Nomo1 mutants show abnormal brain and neuronal development and activation of apoptosis and inflammation-related pathways in the brain. Adult Nomo1-deficient zebrafish exhibit multiple neuropsychiatric behaviors such as hyperactive locomotor activity, social deficits, and repetitive stereotypic behaviors. The Habenular nucleus and the pineal gland in the telencephalon are affected, and the melatonin level of nomo1-/- is reduced. Melatonin treatment restores locomotor activity, reduces repetitive stereotypic behaviors, and rescues the noninfectious brain inflammatory responses caused by nomo1 deficiency. These results suggest melatonin supplementation as a potential therapeutic regimen for neuropsychiatric disorders caused by NOMO1 deficiency.

Evaluation and characterization of starch nanoparticles for adsorption of urea from dialysates.

Starch nanoparticles (SNPs) was produced from type-A, B and C native starches (corn, potato and Trichosanthes kirilowii pulp starches respectively), via the nanoprecipitation method. The SNPs showed different amylose contents, water contact angles, surface morphologies and urea clearance performances. In this work, to examine the parameters of SNPs that may change the urea adsorption capacity, urea adsorption performance in adsorption environments with different pH values, urea concentrations, and adsorption times was examined. Thereafter, the characteristics of SNPs were tested by water contact angle measurements (WCA), transmission electron microscopy, specific surface area measurements, gel permeation chromatography, and zeta potential analysis. The results showed that the Trichosanthes kirilowii pulp (C) SNPs show better adsorption than the corn (A) and potato (B) SNPs. The hydrophobicity of SNPs promotes the urea adsorption of the SNPs. Using grey relational analysis, it was found that WCA and Mn are the critical parameter affecting the adsorption performance, with WCA and Mn within the ranges of 31-33° and 1900-2100 kDa, respectively, were found to be the conditions for optimal urea adsorption.

Single-walled carbon nanohorns-based smart nanotheranostic: From phototherapy to enzyme-activated fluorescence imaging-guided photodynamic therapy.

Phototheranostics, a local non-invasive approach that integrates light-based diagnostics and therapeutics, enables precise treatment using nanotheranostic agents with minimal damage to normal tissues. However, ensuring high-efficiency ablation of cancer cells using phototheranostics for one time irradiation is highly challenging. Herein, we designed and synthesized a single-walled carbon nanohorns-based nanotheranostic agent, HA-IR808-SWNHs, by loading IR808, a photosensitizer, conjugated hyaluronic acid (HA) with an amide bond on the surface of single-walled carbon nanohorns (SWNHs) through noncovalent π-π interaction by the sonication method. The HA in HA-IR808-SWNHs improves the water dispersibility of SWNHs and endows SWNHs with targeting capabilities. Importantly, overexpressed endogenous hyaluronidase in cancer cells actively disassembles HA-IR808-SWNHs, forming small HA-IR808 fragments. The fragments exhibit a strong fluorescence signal and can be used to guide programmed photodynamic therapy for sequentially eliminating the residual living cancer cells. The current study confirms that HA-IR808-SWNHs is an endogenous enzyme-responsive nanotheranostic agent that can be employed to precisely track and ablate residual cancer cells in a spatiotemporal manner. The results strengthen the understanding of SWNH functionalization and expand its potential biomedical application, especially in cancer theranostics.

[Exploring molecular mechanisms of fucoidan in improving human proximal renal tubular epithelial cells aging by targeting autophagy signaling pathways].

Fucoidan(FPS) is an effective component of the Chinese patent medicine named Haikun Shenxi, which treats schronic renal failure in clinics, and has the potential anti-aging effects. However, it is still unclear whether FPS can improve renal aging, especially the molecular mechanism of its anti-aging. The human proximal renal tubular epithelial cells(HK-2) in vitro were divided into normal group(N), D-gal model group(D), low dose of FPS group(L-FPS), high dose of FPS group(H-FPS) and vitamin E group(VE), and treated by the different measures, respectively. More specifically, the HK-2 cells in each group were separately treated by 1 mL of 1% fetal bovine serum(FBS) or D-galactose(D-gal, 75 mmol·L~(-1)) or D-gal(75 mmol·L~(-1))+FPS(25 µg·mL~(-1)) or D-gal(75 mmol·L~(-1))+FPS(50 µg·mL~(-1)) or D-gal(75 mmol·L~(-1))+VE(50 µg·mL~(-1)). After the treatment for 24 h, firstly, the effects of D-gal on senescence-associated ß-galactosidase(SA-ß-gal) staining characteristics and klotho, P53 and P21 protein expression le-vels, as well as adenosine monophosphate activated protein kinase(AMPK)-uncoordinated 51-like kinase 1(ULK1) signaling pathway activation in the HK-2 cells were detected, respectively. Secondly, the effects of FPS and VE on SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal were investigated, respectively. Finally, the effects of FPS and VE on microtubule-associated protein 1 light chain 3(LC3) protein expression level and AMPK-ULK1 signaling pathway activation in the HK-2 cells exposed to D-gal were examined severally. The results indicated that, for the HK-2 cells, the dose of 75 mmol·L~(-1) D-gal could induce the changes of SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels. That is causing cells aging. FPS and VE could both ameliorate the changes of SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal. That is anti-cells aging, here, the functions of FPS and VE are similar. D-gal could not only induce cell aging but also increase LC3Ⅱ, phosphorylated-AMPK(p-AMPK) and phosphorylated-ULK1(p-ULK1) protein expressions, and activate autophagy-related AMPK-ULK1 signaling pathway. FPS and VE could both improve the changes of LC3Ⅱ, p-AMPK and p-ULK1 protein expression levels in the HK-2 cells exposed to D-gal. That is inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. On the whole, for the human proximal renal tubular epithelial cells aging models induced by D-gal, FPS similar to VE, can ameliorate renal cells aging by possibly inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. This finding provides the preliminary pharmacologic evidences for FPS protecting against renal aging.

Exploring molecular mechanisms of fucoidan in improving human proximal renal tubular epithelial cells aging by targeting autophagy signaling pathways / 中国中药杂志

Fucoidan(FPS) is an effective component of the Chinese patent medicine named Haikun Shenxi, which treats schronic renal failure in clinics, and has the potential anti-aging effects. However, it is still unclear whether FPS can improve renal aging, especially the molecular mechanism of its anti-aging. The human proximal renal tubular epithelial cells(HK-2) in vitro were divided into normal group(N), D-gal model group(D), low dose of FPS group(L-FPS), high dose of FPS group(H-FPS) and vitamin E group(VE), and treated by the different measures, respectively. More specifically, the HK-2 cells in each group were separately treated by 1 mL of 1% fetal bovine serum(FBS) or D-galactose(D-gal, 75 mmol·L~(-1)) or D-gal(75 mmol·L~(-1))+FPS(25 μg·mL~(-1)) or D-gal(75 mmol·L~(-1))+FPS(50 μg·mL~(-1)) or D-gal(75 mmol·L~(-1))+VE(50 μg·mL~(-1)). After the treatment for 24 h, firstly, the effects of D-gal on senescence-associated β-galactosidase(SA-β-gal) staining characteristics and klotho, P53 and P21 protein expression le-vels, as well as adenosine monophosphate activated protein kinase(AMPK)-uncoordinated 51-like kinase 1(ULK1) signaling pathway activation in the HK-2 cells were detected, respectively. Secondly, the effects of FPS and VE on SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal were investigated, respectively. Finally, the effects of FPS and VE on microtubule-associated protein 1 light chain 3(LC3) protein expression level and AMPK-ULK1 signaling pathway activation in the HK-2 cells exposed to D-gal were examined severally. The results indicated that, for the HK-2 cells, the dose of 75 mmol·L~(-1) D-gal could induce the changes of SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels. That is causing cells aging. FPS and VE could both ameliorate the changes of SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal. That is anti-cells aging, here, the functions of FPS and VE are similar. D-gal could not only induce cell aging but also increase LC3Ⅱ, phosphorylated-AMPK(p-AMPK) and phosphorylated-ULK1(p-ULK1) protein expressions, and activate autophagy-related AMPK-ULK1 signaling pathway. FPS and VE could both improve the changes of LC3Ⅱ, p-AMPK and p-ULK1 protein expression levels in the HK-2 cells exposed to D-gal. That is inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. On the whole, for the human proximal renal tubular epithelial cells aging models induced by D-gal, FPS similar to VE, can ameliorate renal cells aging by possibly inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. This finding provides the preliminary pharmacologic evidences for FPS protecting against renal aging.

Hypericin-Loaded Carbon Nanohorn Hybrid for Combined Photodynamic and Photothermal Therapy in Vivo.

Photodynamic therapy (PDT) of hypericin (Hyp) is hampered by poor water solubility and photostability. Incorporation of photosensitizers into nanocarriers has been designed to solve these issues. Herein, SWNH-Hyps nanohybrids were first fabricated by loading hypericin on the surface of single-walled carbon nanohorns (SWNHs) through ??? interaction and exhibited high solubility and stability in aqueous water. SWNH-Hyps could be utilized for a single platform for cancer therapy because it could simultaneously generate enough reactive oxygen species and hyperthermia using light irradiation. Moreover, the SWNHs not only improved water solubility, photostability, and therapy effects of Hyp but also protected it from light degradation. SWNH-Hyps could effectively ablate 4T1 cells by photodynamic/photothermal synergistic therapy upon 590 and 808 nm light irradiations compared with PDT. Furthermore, remarkable tumor cell death as well as tumor growth inhibition was proved via photothermal therapy and PDT of SWNH-Hyps under 590 and 808 nm light irradiations, which demonstrated that synergistic anticancer ability of SWNH-Hyps was better than that of free Hyp in vivo. Such a simple and facile adsorption method improved water solubility of Hyp and then enhanced its therapy effect, which displays that SWNHs can be hopefully used in medicines in the future.

Chlorogenic acid in the oxidative stress injury triggered by Shuang-Huang-Lian injection.

Injections of Chinese herbs are a novel approach to prepare traditional Chinese medicines. However, as injections of Chinese herbs have been extensively used, adverse drug reactions (ADRs) have been on the increase. Additionally, the mechanism for injections of Chinese herbs remains unclear. This study explored the potential role played by chlorogenic acid (CGA) in initiating oxidative stress injury triggered by the utilization of injections of Chinese herbs and the underlying mechanism. A total of 90 male Wistar rats were raised for varying periods by using Shuang-Huang-Lian (SHL) injection or CGA in diverse dosages. Western blot analysis examined the expression of nicotinamide adenine dinucleotide phosphate oxidase subunits, spectrophotometry was used to examine the activity taken by catalase, ELISA was used to examine the concentrations of inflammatory factors in serum, and intravital microscopy was employed to examine the microcirculation. The results showed that the excessive peroxide production induced by CGA in high-dose or SHL in the venule walls may well be through nicotinamide adenine dinucleotide phosphate oxidase along with a decline in the activity of catalase, and led to imbalance of basal levels of pro-(TNF-α) and anti-(IL-10) inflammatory cytokines. On the basis of the aforementioned results, the mechanism hidden behind the adverse effects of CGA induced by irrational use of Chinese herbal injection can be identified from a deeper perspective.

Supercharged fluorescent protein functionalized water-soluble poly(N-phenylglycine) nanoparticles for highly effective imaging-guided photothermal therapy.

We describe the development of supercharged fluorescent protein modified water-soluble poly(N-phenylglycine) nanoparticles (SPNPG/ScGFP) as a novel nanotheranostic agent with highly effective cell penetration for image-guided photothermal cancer therapy.

Asthma at acute attack stage treated with "Shao's five needling therapy": a multi-central randomized controlled study / 中国针灸

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of asthma at acute attack stage treated with "Shao's five needling therapy".</p><p><b>METHODS</b>The randomized controlled method was applied to divide 210 cases into an observation group and a control group, 105 cases in each one. In the observation group, "Shao's five needling therapy" [Feishu (BL 13), Dazhui (GV 14), Fengmen (BL 12)] and the combined therapy were adopted, including oxygen uptake, aerosol inhalation and oral administration of prednisone. In the control group, the oral administration of theophylline sustained release tablet and the combined therapy were applied. The treatment was continued for 7 days. The clinical symptoms and physical signs such as wheezing, cough, expectoration, chest stuffiness, wheezing rale and shortness of breath, as well as lung function indices such as forced expiratory volume one second (FEV1) and peak expiratory flow (PEF) were observed before and after treatment in the two groups.</p><p><b>METHODS</b>In the observation group, 69 cases were cured clinically, 20 cases effective remarkably, 7 cases effective and 0 case failed. In the control group, 49 cases were cured clinically, 31 cases effective remarkably, 15 cases effective and 0 case failed. The difference in the efficacy was significant in comparison of the two groups (P < 0.05). The therapeutic effect in the observation group was better than that in the control group. The total score of the symptoms and physical signs, FEV1 and PEF after treatment were all improved significantly in the two groups (all P < 0.01). And the results in the observation group were better than those in the control group (all P < 0.01).</p><p><b>CONCLUSION</b>"Shao's five needling therapy" achieves the significant efficacy on asthma at acute attack stage. It significantly relieves the symptoms and physical signs of the patients and improves lung functions. The effect is better than that of theophylline sustained release tablet.</p>

[Experimental study of eliminat dampness resolv phlegm method in treating cervical spondylopathy of the vertebral artery type].

OBJECTIVE: To detect the velocity and viscosity of blood flow of the vertebral arteries, the apoptotic cell and apoptotic related protein in the brain in order to offer theoretical foundation for the treatment of cervical spondylopathy of the vertebral artery type with the eliminat dampness resolv phlegm method. METHODS: Sixty male Japanese big ear rabbits were divided randomly into normal sodium group (A), Flunarizine group (B), low dosage Wendantang group (C), large dosage Wendantang group (D), Flunarizine group combined with large dosage Wendantang group (E), normal group (F). Each group had 10 rabbits. Xiaozhiling injection was injected around the vertebral arteries of rabbits in group A, B C, D, E to make the model of the cervical spondylopathy of the vertebral artery type. Normal sodium (20 ml x kg(-1)d(-1)) was apply through intragastric administration in group A, F; Flunarizine (0.8 mg x kg(-1)d(-1)), low dosage Wendantang (1 g x ml(-1)d(-1)), large dosage Wendantang (2 g x ml(-1)d(-1)), Flunarizine combined with large dosage Wendantang were respectively apply through intragastric administration in group B, C, D, E. The velocity and viscosity of blood flow of the vertebral arteries, the apoptotic cell and apoptotic protein in the brain were detected before and after the treatment. RESULTS: Satisfactory animal model were obtained in group A, B, C, D, E. The rabbits of group E had the most improvement of the velocity and viscosity of blood flow of the vertebral arteries while at meantime, which had the lowest apoptotic index and apoptotic related protein expression in the brain. CONCLUSION: The routine treatment for the cervical spondylopathy of the vertebral artery combined with eliminat dampness resolv phlegm method could improve velocity and viscosity of blood flow of the vertebral arteries, which maybe relate with reduction of apoptosis in the brain.

Experimental study of eliminat dampness resolv phlegm method in treating cervical spondylopathy of the vertebral artery type / 中国骨伤

<p><b>OBJECTIVE</b>To detect the velocity and viscosity of blood flow of the vertebral arteries, the apoptotic cell and apoptotic related protein in the brain in order to offer theoretical foundation for the treatment of cervical spondylopathy of the vertebral artery type with the eliminat dampness resolv phlegm method.</p><p><b>METHODS</b>Sixty male Japanese big ear rabbits were divided randomly into normal sodium group (A), Flunarizine group (B), low dosage Wendantang group (C), large dosage Wendantang group (D), Flunarizine group combined with large dosage Wendantang group (E), normal group (F). Each group had 10 rabbits. Xiaozhiling injection was injected around the vertebral arteries of rabbits in group A, B C, D, E to make the model of the cervical spondylopathy of the vertebral artery type. Normal sodium (20 ml x kg(-1)d(-1)) was apply through intragastric administration in group A, F; Flunarizine (0.8 mg x kg(-1)d(-1)), low dosage Wendantang (1 g x ml(-1)d(-1)), large dosage Wendantang (2 g x ml(-1)d(-1)), Flunarizine combined with large dosage Wendantang were respectively apply through intragastric administration in group B, C, D, E. The velocity and viscosity of blood flow of the vertebral arteries, the apoptotic cell and apoptotic protein in the brain were detected before and after the treatment.</p><p><b>RESULTS</b>Satisfactory animal model were obtained in group A, B, C, D, E. The rabbits of group E had the most improvement of the velocity and viscosity of blood flow of the vertebral arteries while at meantime, which had the lowest apoptotic index and apoptotic related protein expression in the brain.</p><p><b>CONCLUSION</b>The routine treatment for the cervical spondylopathy of the vertebral artery combined with eliminat dampness resolv phlegm method could improve velocity and viscosity of blood flow of the vertebral arteries, which maybe relate with reduction of apoptosis in the brain.</p>

[Effects of Xianling Gubao capsules for the treatment of bone loss induced by glucocorticoid].

OBJECTIVE: To study the clinical effects of Xianling Gubao capsules for the treatment of glucocorticoid-induced osteoporosis. METHODS: From 2005.6 to 2007.8, 50 patients with primary glomerulonephritis treated with glucocorticoids were divided into two groups randomly. The treatment group were dealed with Xianling Gubao capsules and the control group with calcitriol and Caltrate D 600. TCM Synrdome integral before and after treatment were estimated. And the bone mineral density (BMD) of lumbar spine and femoral neek was measured by dual-energy X-ray absorptionm etry (DEXA). Osteo-calcin, intact parathyroidhormone (IPTH), urine excretion of calcium and phosphorus, serum calcium and phosphorus were detected before and after treatment, and adverse effects were investigated too. RESULTS: TCM Synrdome integral in two groups decresed apparently (P<0.05), which decresed more apparently in the treatment group than that in control group (P<0.05). BMD of lumbar spine and femoral neek increased in two groups (P<0.05), but there were no statistical deferences between them (P>0.05). Serum osteocalcin after treatment reduced significantly in two groups (P<0.05) compared with pre-treatment,but there were no statistical deferences between the treatment and the control group (P>0.05). In the control group, serum calcium after treatment increased significantly (P<0.05), but there were no statistical deferences compared with the treatment group (P>0.05). There were no statistical deferences in intact parathyroidhormone, urine excretion of calcium and phosphorus, serum phosphorus in the treatment and the control group before and after therapy. CONCLUSION: Both the treatment group and the control group have clinical effects in prevention and treatment of GC-induced osteoporosis, but the treatment group has more remarkable therapeutic effect and less adverse effects.

Effects of Xianling Gubao capsules for the treatment of bone loss induced by glucocorticoid / 中国骨伤

<p><b>OBJECTIVE</b>To study the clinical effects of Xianling Gubao capsules for the treatment of glucocorticoid-induced osteoporosis.</p><p><b>METHODS</b>From 2005.6 to 2007.8, 50 patients with primary glomerulonephritis treated with glucocorticoids were divided into two groups randomly. The treatment group were dealed with Xianling Gubao capsules and the control group with calcitriol and Caltrate D 600. TCM Synrdome integral before and after treatment were estimated. And the bone mineral density (BMD) of lumbar spine and femoral neek was measured by dual-energy X-ray absorptionm etry (DEXA). Osteo-calcin, intact parathyroidhormone (IPTH), urine excretion of calcium and phosphorus, serum calcium and phosphorus were detected before and after treatment, and adverse effects were investigated too.</p><p><b>RESULTS</b>TCM Synrdome integral in two groups decresed apparently (P<0.05), which decresed more apparently in the treatment group than that in control group (P<0.05). BMD of lumbar spine and femoral neek increased in two groups (P<0.05), but there were no statistical deferences between them (P>0.05). Serum osteocalcin after treatment reduced significantly in two groups (P<0.05) compared with pre-treatment,but there were no statistical deferences between the treatment and the control group (P>0.05). In the control group, serum calcium after treatment increased significantly (P<0.05), but there were no statistical deferences compared with the treatment group (P>0.05). There were no statistical deferences in intact parathyroidhormone, urine excretion of calcium and phosphorus, serum phosphorus in the treatment and the control group before and after therapy.</p><p><b>CONCLUSION</b>Both the treatment group and the control group have clinical effects in prevention and treatment of GC-induced osteoporosis, but the treatment group has more remarkable therapeutic effect and less adverse effects.</p>