[Expert consensus on integrated traditional Chinese and western medicine diagnosis and treatment for osteoporotic fractures].

Osteoporotic fractures represent the most severe complications of osteoporosis,characterized by insidious onset,high mortality and disability rates,and a steadily increasing incidence,imposing a significant socioeconomic burden. Western medicine has advantages in diagnosis and surgical interventions,while traditional Chinese medicine excels in holistic management and the restoration of bodily equilibrium. The integration of both traditional Chinese medicine (TCM) and western medicine emerges as an effective therapeutic strategy for osteoporotic fractures. In order to propagate the concept of integrated diagnosis and treatment,foster the advancement of integrated medical techniques for osteoporotic fractures,and establish standardized and normative protocols for disease prevention,diagnosis,and treatment,a consensus expert group,led by Geriatric Branch of Chinese Geriatrics Society,the Young Osteoporosis Group of Orthopedics Branch of Chinese Medical Association,Osteoporosis Group of Orthopedics Branch of Chinese Physician Association,and Osteoporosis Professional Committee of the Shanghai Society of Integrated Traditional Chinese and Western Medicine,was established. This group engaged in deliberations and formulated the "Expert Consensus on Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Osteoporotic Fractures" elucidating the concept of integrated medicine and offering recommendations in the domains of prevention,diagnosis,and treatment,with the aspiration of ameliorating the prognosis of osteoporotic fractures and enhancing the quality of life for these patients.

Dietary Achievable Dose of Protocatechuic Acid, a Metabolite of Flavonoids, Inhibits High-Fat Diet-Induced Obesity in Mice.

SCOPE: Protocatechuic acid (PCA), a gut microbiota metabolite of flavonoids, inhibits dietary obesity and increases uncoupling protein 1 (UCP1), a critical regulator responsible for adipose thermogenesis; however, these effects are achieved at dietary unachievable (pharmacological) dose. It evaluates whether dietary achievable dose of PCA inhibits adiposity by activating adipose thermogenesis. METHODS AND RESULTS: Six-week-old male C57BL/6J mice are fed a high-fat diet (HFD) alone (control) or supplemented with 0.003% PCA w/w for 16 weeks. PCA consumption does not affect food intake but appreciably reduces body weight gain, improves insulin sensitivity, and attenuates hepatic steatosis. These effects are associated with no significant changes in the abundance of UCP1 in adipose tissues. Instead, PCA consumption increases the abundance and enzymatic activity of carnitine palmitoyltransferase 1 (the first rate-limiting enzyme in fatty acid oxidation) in the livers, inguinal white, and brown adipose tissues. Surprisingly, PCA at physiologically achievable dose does not affect the abundance and enzymatic activity of carnitine acyltransferase-1 expression and the capacity of fatty acid oxidation in 3T3-L1-derived white or brown adipocytes and human hepatoma HepG2 cells. CONCLUSIONS: Dietary achievable dose of PCA attenuates HFD-induced adiposity, which is likely achieved by increasing fatty acid oxidation other than activating adipose thermogenesis.

Betaine Supplementation Attenuates S-Adenosylhomocysteine Hydrolase-Deficiency-Accelerated Atherosclerosis in Apolipoprotein E-Deficient Mice.

S-adenosylhomocysteine (SAH) is a risk factor of cardiovascular diseases and atherosclerosis. However, the causal association between SAH and atherosclerosis is still uncertain. In the present study, heterozygous SAH hydrolase (SAHH+/-) knockout mice were bred with apolipoprotein E-deficient mice to produce ApoE-/-/SAHH+/- mice. At 8 weeks of age, these mice were fed on AIN-93G diets added with or without betaine (4 g betaine/100 g diet) for 8 weeks. Compared with ApoE-/-/SAHHWT mice, SAHH deficiency caused an accumulation of plasma SAH concentration and a decrease in S-adenosylmethionine (SAM)/SAH ratio as well as plasma homocysteine levels. Betaine supplementation lowered SAH levels and increased SAM/SAH ratio and homocysteine levels in ApoE-/-/SAHH+/- mice. Furthermore, SAHH deficiency promoted the development of atherosclerosis, which was reduced by betaine supplementation. The atheroprotective effects of betaine on SAHH-deficiency-promoted atherosclerosis were associated with inhibition of NFκB inflammation signaling pathway and inhibition of proliferation and migration of smooth muscle cells. In conclusion, our results suggest that betaine supplementation lowered plasma SAH levels and protected against SAHH-deficiency-promoted atherosclerosis through repressing inflammation and proliferation and migration of smooth muscle cells.

Natural lactucopicrin alleviates importin-α3-mediated NF-κB activation in inflammated endothelial cells and improves sepsis in mice.

Lactucopicrin, a bitter sesquiterpene lactone of leafy vegetables, such as chicory, curly escarole, and lettuce, possesses anti-malarial, anti-cancer and analgesic properties. However, it remains unknown whether lactucopicrin could inhibit vascular endothelial nuclear factor-κB (NF-κB) activation, a hallmark of vascular inflammatory diseases including sepsis. In tumor necrosis factor-α-stimulated human or mouse aortic endothelial cells, lactucopicrin dose-dependently inhibited NF-κB activation, and concomitantly repressed both vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)-mediated monocyte adhesion. The lactucopicrin effect was not due to modulation of inhibitor of NF-κB kinases (IKK) α/ß/γ, inhibitor of NF-κB alpha (IκBα), and NF-κB/p65 DNA binding activity. Instead, lactucopicrin inhibited importin-α3 expression by destabilization of its mRNA, an effect mediating the lactucopicrin effect on NF-κB activity. More importantly, in lipopolysaccharide (LPS)-elicited septic mice, oral gavage with lactucopicrin decreased mortality by 30.5% as compared with the control treatment. This effect was associated with inhibited importin-α3 expression, suppressed NF-κB activation and VCAM-1/ICAM-1 expression, and inhibited leukocyte influx in the vascular endothelium of both lung and aorta. Collectively, our novel data suggest that dietary supplementation with lactucopicrin inhibits endothelial NF-κB activation by down-regulation of importin-α3 and thereby improves sepsis.

Feasibility of Adjunctive Bright Light Therapy for Depressive Symptoms on an Acute Psychiatric Floor.

BACKGROUND: Bright light therapy (BLT) has been increasingly used as an experimental treatment in non-seasonal unipolar depression. While clinical trials have demonstrated the efficacy of BLT in ameliorating depression for outpatients, studies examining BLT in the psychiatric inpatient setting are currently lacking. AIM: The purpose of this study is to explore whether BLT as adjunctive treatment for depressive symptoms on an acute psychiatric floor is feasible and explore associated changes in depressive symptoms. METHODS: An observational, cross-sectional study was conducted at State University of New York (SUNY) Upstate 4B acute inpatient psychiatric unit. BLT was administered to participating patients as adjunctive therapy to their psychopharmacological and psychotherapy treatments on a daily basis throughout their hospitalization. Beck Depression Inventory-II (BDI-II), Hamilton Rating Scale for Depression (HAM-D), and Outcome Questionnaire-45.2 (OQ-45.2) were administered before commencing BLT and after their last BLT session. Changes to the aforementioned measures before and after BLT treatment, the dose response of measure changes based on number of sessions, and the hospital length of stay along with the secondary factors such as age, gender, other psychiatric comorbidities, social factors, and psychiatric medications were analyzed. RESULTS:  BLT is feasible on acute psychiatric inpatient floor with adherence of 94% and has very few side effects. The repeated measures of depression and functioning demonstrated significant decrease in depression and improvement in functioning. Although not statistically significant, clinical meaningful dose-response relationship was found between a number of BLT sessions and improvement in depressive symptoms with five BLT sessions being an optimal amount for depression amelioration. CONCLUSION: BLT combined with the ongoing psychopharmacological treatment was well tolerated and easy to administer. It offers a simple, safe, and cost-effective approach to augmenting depressive treatment on an acute psychiatric floor.

Integration of electrochemical and calcium hypochlorite oxidation for simultaneous sludge deep dewatering, stabilization and phosphorus fixation.

A hybrid electrochemical process with Ca(ClO)2 addition for simultaneous sludge dewaterability, stabilization and phosphorus fixation was proposed. Under optimal conditions (150 mg/g VS Ca(ClO)2, 15 V), the capillary suction time (CST) and specific resistance to filtration (SRF) were decreased by 88% and 92%, respectively. Efficient sludge stabilization with E. coli colonies of less than 1000 MPN/g TS was achieved. Phosphorus of 99% was removed from the filtrate and successfully fixed in the sludge cake and on the electrode surface. The integration of electrochemical and hypochlorite oxidation could effectively degrade the tightly bound extracellular polymeric substances (TB-EPS) structure with a total organic carbon (TOC) reduction of 52%. Besides, the disintegration of microbial cell envelopes was also achieved, with a reduction of living cell fraction of 98%. Furthermore, system pH could be maintained at near neutral (7.45) and the conversion of Fe(II) to Fe(III) was also facilitated with the addition of Ca(ClO)2, resulting in improved electrocoagulation process for enhanced sludge dewatering and phosphorus fixation. The multifunctional effects were achieved with the cooperated extracellular electrooxidation for EPS destruction and the active chlorine for intracellular microbial cell disintegration. This research provides a promising strategy for integrated sludge treatment and recycling for possible land utilization.

Diagnosis and treatment of an elderly patient with 2019-nCoV pneumonia and acute exacerbation of chronic obstructive pulmonary disease in Gansu Province: A case report.

BACKGROUND: In December 2019, the first patient with 2019-novel coronavirus (2019-nCoV) was reported in Wuhan, China, and the disease spread rapidly across the country and surrounding countries within 2 mo. As of February 29, 2020, a total of 91 confirmed cases had been reported in Gansu Province. This case report of the diagnosis and treatment of an elderly patient with 2019-nCoV pneumonia complicated by acute exacerbation of chronic obstructive pulmonary disease in Gansu Province aims to provide a better reference for the treatment of patients in the future. CASE SUMMARY: The patient, a 94-year-old female, lived in Maiji District of Tianshui, Gansu Province, China. On January 30, 2020, she was admitted to the Fourth People's Hospital of Tianshui after 9 d of close contact with a patient with 2019-nCoV pneumonia. She was subsequently admitted to Gansu Provincial Hospital of Traditional Chinese Medicine for isolation and transferred to Tianshui Gansu Provincial Hospital of Infectious Diseases on February 3, 2020 for treatment. Upon initial examination, her body temperature was 36.7 °C , pulse was 80, breathing was 20, and blood pressure was 130/80 mmHg. She was conscious with normal development and normal nutrition. The pharynx was not red, and bilateral tonsils were not red and swollen. The lungs sounded slightly coarse with no dry or wet rales. The first symptoms were cough and fatigue on 2 February. The patient was hospitalized for 12 d. After active treatment, she was discharged on February 14 with a good prognosis. CONCLUSION: A history of exposure to the affected area or patient is a major cause of 2019-nCoV infection, and population clustering is a high risk factor for transmission. Patients may not necessarily have respiratory system symptoms as the only clinical manifestation but may also have concomitant or first onset digestive symptoms. Attention should be paid to the prevention and treatment of multiple organ dysfunction syndrome. Nucleic acid testing is extremely important and needs to be repeated several times. Laboratory and auxiliary examination indicators during the first week of admission are extremely important. It is feasible to carry out dynamic and continuous index monitoring, which can predict and guide the prevention and treatment of multiple organ dysfunction and the prognosis of the disease.

Protocatechuic Acid Inhibits Vulnerable Atherosclerotic Lesion Progression in Older Apoe-/- Mice.

BACKGROUND: Normalization of arterial inflammation inhibits atherosclerosis. The preventive role for protocatechuic acid (PCA) in early-stage atherosclerosis is well recognized; however, its therapeutic role in late-stage atherosclerosis remains unexplored. OBJECTIVE: We investigated whether PCA inhibits vulnerable atherosclerosis progression by normalizing arterial inflammation. METHODS: Thirty-wk-old male apolipoprotein E-deficient (Apoe-/-) mice with vulnerable atherosclerotic lesions in the brachiocephalic artery were fed the AIN-93G diet alone (control) or supplemented with 0.003% PCA (wt:wt) for 20 wk. Lesion size and composition, IL-1ß, and NF-κB in the brachiocephalic arteries, and serum lipid profiles, oxidative status, and proinflammatory cytokines (e.g., IL-1ß, monocyte chemoattractant protein-1, and serum amyloid A) were measured. Moreover, the effect of PCA on the inflammation response was evaluated in efferocytic macrophages from C57BL/6J mice. RESULTS: Compared with the control treatment, dietary PCA supplementation significantly reduced lesion size (27.5%; P < 0.05) and also improved lesion stability (P < 0.05) as evidenced by increased thin fibrous cap thickness (31.7%) and collagen accumulation (58.3%), reduced necrotic core size (37.6%) and cellular apoptosis (73.9%), reduced macrophage accumulation (45.1%), and increased vascular smooth muscle cell accumulation (51.5%). Moreover, PCA supplementation inhibited IL-1ß expression (53.7%) and NF-κB activation (64.4%) in lesions. However, PCA supplementation did not change serum lipid profiles, total antioxidant capacity, and inflammatory cytokines. In efferocytic macrophages, PCA at 0.5 and 1 µmol/L inhibited Il1b/IL-1ß mRNA (27.2-46.5%) and protein (29.2-49.6%) expression and NF-κB activation (67.0-80.3%) by upregulation of MER proto-oncogene tyrosine kinase (MERTK) and inhibition of mitogen-activated protein kinase 3/1 (MAPK3/1). Strikingly, the similar pattern of the MERTK and MAPK3/1 changes in lesional macrophages of mice after PCA intervention in vivo was recapitulated. CONCLUSION: PCA inhibits vulnerable lesion progression in mice, which might partially be caused by normalization of arterial inflammation by upregulation of MERTK and inhibition of MAPK3/1 in lesional macrophages.

Dezhou donkey (Equus asinus) milk a potential treatment strategy for type 2 diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: Donkey (Equus asinus) milk has become a medical and nutrient product since ancient times. In addition, donkey milk was regarded as a medicinal food and substitute product for infant formula in some ancient western countries. Chinese ancient medical books documented the medicinal value of donkey milk, using donkey milk to treat diabetes, cough and jaundice. AIM OF THE STUDY: To investigate the donkey milk's components and anti-diabetic effect of donkey milk in vitro and in vivo and to study the molecular mechanism of donkey milk was an anti-diabetic medication. MATERIALS AND METHODS: In this study, the gastrointestinal digested donkey milk was simulated in vitro and its products of protein digestion were analyzed by SDS-PAGE. We then performed cell viability assay, insulin secretion assay, animal experiments and ELISA assays to study the anti-diabetic effect of donkey milk in vitro and in vivo. Donkey milk's anti-diabetic molecular mechanism and specific targets were detected by using quantitative real time PCR. RESULTS: Lysozyme (LZ) and α-lactalbumin (α-La) exhibited significantly lower digestibility and higher retention than the other components of donkey milk. In vitro, 500 µg/mL of donkey milk could improve damaged ß-cells viability significantly (P < 0.0001). In vivo, the blood glucose and HOMA-IR of diabetic rats treated with donkey milk were 14.23 ±â€¯5.18 mM and 74.94 ±â€¯23.62, respectively, whereas the diabetic group were 22.18 ±â€¯2.23 mM and 112.16 ±â€¯18.44, respectively (P < 0.01). The SOD value of donkey milk group was 265.87 ±â€¯21.29 U/L, while the SOD value of diabetic group was 193.20 ±â€¯52.07 U/L (P < 0.05). These results indicated that the blood glucose was reduced, the ability of the body to eliminate free radicals was enhanced, antioxidant levels in the body was increased, insulin resistance was improved in type 2 diabetic rats after donkey milk powder fed for 4 weeks. Furthermore, donkey milk could treat diabetes through down-regulating phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose-6-phosphatase (G6PC). CONCLUSIONS: Donkey milk has played an important role in the treatment of type 2 diabetes, and contributed to the development of the donkey milk products.

Laser-Induced Transformable BiS@HSA/DTX Multiple Nanorods for Photoacoustic/Computed Tomography Dual-Modal Imaging Guided Photothermal/Chemo Combinatorial Anticancer Therapy.

Suboptimal intratumor accumulation and poorly controllable release of encapsulated drugs remain unresolved challenges hampering further advancement of nanomedicines in cancer therapy. Herein, we conceived near-infrared (NIR) laser-triggered transformable BiS@HSA/DTX multiple nanorods (mNRs), which were made of small bundles of bismuth sulfide nanorods (BiS NRs) coated with docetaxel (DTX)-inlaid human serum albumin (HSA). The BiS@HSA/DTX mNRs had a lateral size of approximately 100 nm and efficiently accumulated in the tumor microenvironment upon systemic administration in tumor-bearing nude mice. NIR laser irradiation of the tumor area caused rapid disassembly of the BiS@HSA/DTX mNRs into individual HSA-coated BiS nanorods (BiS@HSA iNRs) and triggered the release of DTX from the HSA corona, due to the local temperature increase generated by BiS NRs via the photothermal effect. The laser-induced transformation into BiS@HSA iNRs facilitated their penetration and increased the retention time in tumor. The spatiotemporal delivery behavior of the BiS@HSA/DTX mNRs could be monitored by photoacoustic/computed tomography dual-modal imaging in vivo. Furthermore, because of the excellent photothermal conversion properties of BiS NRs and laser-triggered DTX release from BiS@HSA/DTX mNRs, efficient tumor combinatorial therapy was achieved via concurrent hyperthermia and chemotherapy in mice treated with BiS@HSA/DTX mNRs upon NIR laser irradiation.

Thermally Triggered in Situ Assembly of Gold Nanoparticles for Cancer Multimodal Imaging and Photothermal Therapy.

The assembly of gold nanoparticles (AuNPs) to AuNP assemblies is of interest for cancer therapy and imaging. Herein we introduce a new and general paradigm, thermally triggered AuNP assembly, for the development of novel intelligent platforms for cancer photothermal therapy (PTT) and multimodal imaging. Site-specific conjugation of a thermally sensitive elastin-like polypeptide (ELP) to AuNPs yields thermally sensitive ELP-AuNPs. Interestingly, ELP-AuNPs can in situ form AuNP assemblies composed of short necklace-like gold nanostructures at elevated temperatures and thus show strong near-infrared light absorption and high photothermal effect. These thermally responsive properties of ELP-AuNPs enable simultaneous photothermal/photoacoustic/X-ray computed tomographic imaging and PTT of melanoma after single intratumoral injection of ELP-AuNPs. The thermally triggered assembly of a variety of nanoparticles with optical, electronic, and magnetic properties into nanoparticle assemblies may open new ways for the establishment of intelligent platforms for various applications in biomedicine.

Near-Infrared Emission CuInS/ZnS Quantum Dots: All-in-One Theranostic Nanomedicines with Intrinsic Fluorescence/Photoacoustic Imaging for Tumor Phototherapy.

Many theranostic nanomedicines (NMs) have been fabricated by packaging imaging and therapeutic moieties together. However, concerns about their potential architecture instability and pharmacokinetic complexity remain major obstacles to their clinical translation. Herein, we demonstrated the use of CuInS/ZnS quantum dots (ZCIS QDs) as "all-in-one" theranostic nanomedicines that possess intrinsic imaging and therapeutic capabilities within a well-defined nanostructure. ZCIS QDs were exploited for multispectral optical tomography (MSOT) imaging and synergistic PTT/PDT therapy. Due to the intrinsic fluorescence/MSOT imaging ability of the ZCIS QDs, their size-dependent distribution profiles were successfully visualized at tumor sites in vivo. Our results showed that the smaller nanomedicines (ZCIS NMs-25) have longer tumor retention times, higher tumor uptake, and deeper tumor penetration than the larger nanomedicines (ZCIS NMs-80). The ability of ZCIS QDs to mediate photoinduced tumor ablation was also explored. Our results verified that under a single 660 nm laser irradiation, the ZCIS NMs had simultaneous inherent photothermal and photodynamic effects, resulting in high therapy efficacy against tumors. In summary, the ZCIS QDs as "all-in-one" versatile nanomedicines allow high therapeutic efficacy as well as noninvasively monitoring tumor site localization profiles by imaging techniques and thus hold great potential as precision theranostic nanomedicines.

Rapid Degradation and High Renal Clearance of Cu3BiS3 Nanodots for Efficient Cancer Diagnosis and Photothermal Therapy in Vivo.

A key challenge for the use of inorganic nanomedicines in clinical applications is their long-term accumulation in internal organs, which raises the common concern of the risk of adverse effects and inflammatory responses. It is thus necessary to rationally design inorganic nanomaterials with proper accumulation and clearance mechanism in vivo. Herein, we prepared ultrasmall Cu3BiS3 nanodots (NDs) as a single-phased ternary bimetal sulfide for photothermal cancer therapy guided by multispectral optoacoustic tomography (MSOT) and X-ray computed tomography (CT) due to bismuth's excellent X-ray attenuation coefficient. We then monitored and investigated their absorption, distribution, metabolism, and excretion. We also used CT imaging to demonstrate that Cu3BiS3 NDs can be quickly removed through renal clearance, which may be related to their small size, rapid chemical transformation, and degradation in an acidic lysosomal environment as characterized by synchrotron radiation-based X-ray absorption near-edge structure spectroscopy. These results reveal that Cu3BiS3 NDs act as a simple but powerful "theranostic" nanoplatform for MSOT/CT imaging-guided tumor ablation with excellent metabolism and rapid clearance that will improve safety for clinical applications in the future.

Trichosanthin suppresses the proliferation of glioma cells by inhibiting LGR5 expression and the Wnt/ß-catenin signaling pathway.

Studies have indicated that trichosanthin (TCS), a bioactive protein extracted and purified from the tuberous root of Trichosanthes kirilowii (a well­known traditional Chinese medicinal plant), produces antitumor effects on various types of cancer cells. However, the effects of TCS on glioma cells are poorly understood. The objective of this study was to investigate the antitumor effects of TCS on the U87 and U251 cell lines. The in vitro effects of TCS on these two cell lines were determined using a Cell Counting Kit­8 (CCK­8) assay, Annexin V­FITC staining, DAPI staining, Transwell assays, terminal deoxynucleotidyl transferase­mediated dUTP nick end­labeling (TUNEL) assays, 5,5',6,6'­tetrachloro­1,1',3,3'­tetraethyl­imidacarbocyanine iodide (JC­1) staining and western blotting, which was utilized to assess the expression of leucine­rich repeat­containing G protein­coupled receptor 5 (LGR5) and key proteins in the Wnt/ß­catenin signaling pathway. Our data indicated that TCS inhibited the proliferation of glioma cells in a dose­ and time­dependent manner and played a role in inhibiting glioma cell invasion and migration. Additional investigation revealed that the expression levels of LGR5 and of key proteins in the Wnt/ß­catenin signaling pathway were markedly decreased after TCS treatment. The results suggest that TCS may induce apoptosis in glioma cells by targeting LGR5 and repressing the Wnt/ß­catenin signaling pathway. In the future, in vivo experiments should be conducted to examine the potential use of this compound as a novel therapeutic agent for gliomas.

Chemical constituents and bioactivities of Panax ginseng (C. A. Mey.).

Ginseng, Panax ginseng (C. A. Mey.), is a well-known Chinese traditional medicine in the Far East and has gained popularity in the West during the last decade. There is extensive literature on the chemical constituents and bioactivities of ginseng. In this paper we compiled the chemical constituents isolated and detected from ginseng including polysaccharides, ginsenosides, peptides, polyacetylenic alcohols, fatty acids, etc. Meanwhile we summarized the biological activities of ginseng, which have been reported over the past few decades, including: anti-aging activity, anti-diabetic activity, immunoregulatory activity, anti-cancer activity, neuroregulation activity, wound and ulcer healing activity, etc. Nevertheless, further studies to exploit other kinds of constituents and new biological activities of ginseng are still necessary to facilitate research and development in the future.

[Study on action mechanism of adjuvant therapeutic effect compound Ejiao slurry in treating cancers based on network pharmacology].

Recently, compound Ejiao slurry (FFEJJ) had been applied to treat cancer patients in clinic, with obvious curative effect. In this study, data and literatures were collected from the TCM chemical component database to establish the chemical component database of FFEJJ. Afterwards, MetaDrug software was used to predict the targets of FFEJJ and obtain the compound-target network. Next, the compound-target network was compared and analyzed to obtain the "compound-target-tumor target" heterogeneous network. Besides, further analysis was made on gene functions and metabolic pathway. The results indicated that FFEJJ could directly resist tumors by regulating cancer cell differentiation, growth, proliferation and apoptosis, and show an adjuvant therapeutic effect by enriching the blood and increasing the immunity.

Chemical constituents and bioactivities of Colla corii asini.

In China, Colla corii asini is a health-care food and traditional Chinese medicine widely used in life-nourishing and clinical hematic antanemic therapy for more than 2,000 years. In this paper we compiled the chemical constituents isolated and detected from Colla corii asini including amino acids, proteins/gelatins, polysaccharides, volatile substances, inorganic substances, etc. Meanwhile we investigated the biological activities of Colla corii asini, which have been reported over the past few decades, including, hematologic diseases inhibitory activities, anti-aging activity, antitumor activity, immunomodulatory activity, bone repair activity, anti-inflammatory activity, antifatigue activity, etc. However, few reports on the relationships between the chemical constituents and bioactivities have been found, further studies of Colla corii asini are still necessary to facilitate research and development in the future.

Hematopoietic effects and mechanisms of Fufang e׳jiao jiang on radiotherapy and chemotherapy-induced myelosuppressed mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang e׳jiao jiang (FEJ), which has been widely used in clinic to replenish qi (vital energy) and nourish blood, is a famous traditional Chinese medicine formula made up of Colla corii asini (donkey-hide gelatin prepared by stewing and concentrating from the hide of Equus asinus Linnaeus.), Radix codonopsis pilosulae (the root of Codonopsis pilosula (Franch.) Nannf.), Radix ginseng rubra (the steamed and dried root of Panax ginseng C.A. Mey.), Fructus crataegi (the fruit of Crataegus pinnatifida Bunge) and Radix rehmanniae preparata (the steamed and sun dried tuber of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey.). The present study aimed to investigate the hematopoietic effects of FEJ on myelosuppressed mice induced by radiotherapy and chemotherapy systematically and to explore the underlying hematopoietic regulation mechanisms. METHODS: The myelosuppressed mouse model was induced by (60)Co radiation, cyclophosphamide and chloramphenicol. FEJ was then administered by i.g. at the dosages of 5, 10, or 20 mL/kg·d for 10d. The numbers of blood cells from peripheral blood and bone marrow nucleated cells (BMNC) were counted. Body weight and the thymus and spleen indices were also measured. The numbers of hemopoietic progenitor cells and colony-forming unit-fibroblast (CFU-F) were measured in vitro. The ratio of hematopoietic stem cells (HSC) in BMNC, cell cycle and apoptosis of BMNC were determined by flow cytometry. The histology of femoral bone was examined by H&E staining. The levels of transforming growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α), erythropoietin (EPO), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) and interleukin-6 (IL-6) in serum were measured by ELISA. IL-1ß, IL-3, IL-6 mRNA levels in spleen were detected by real-time quantitative PCR (RT-qPCR). In addition, bone marrow stromal cells (BMSC) were cultured in vitro followed by treatment with different doses of FEJ (2.5, 5, 10 µL/mL) for 48 h. Then the levels of cytokines (IL-6, SCF, GM-CSF) in the conditioned media and their mRNA levels in BMSC were determined by ELISA and RT-qPCR, respectively. RESULTS: FEJ could significantly increase the numbers of peripheral blood cells and BMNC, and reverse the loss of body weight and the atrophy of thymus and spleen in a dose-dependent manner. The quantities of hemopoietic progenitor cells and CFU-F in bone marrow were also significantly increased in a dose-dependent manner after FEJ administration. A high-dose FEJ of 20 mL/kg·d could significantly increase the ratio of HSC in BMNC, promote bone marrow cells entering the proliferative cycle phase (S+G2/M) and prevent cells from proceeding to the apoptotic phase. FEJ could also improve the femoral bone marrow morphology. Furthermore, FEJ could increase the levels of GM-CSF and IL-3 and reduce the level of TGF-ß in serum, and enhance the expressions of IL-1ß and IL-3 mRNA in spleen. Lastly, the levels of cytokines (IL-6, SCF, GM-CSF) in the conditioned media and their mRNA levels in BMSC were elevated after treatment with FEJ. CONCLUSIONS: FEJ was clearly confirmed to promote the recovery of bone marrow hemopoietic function in a myelosuppressed mouse model, which may be attributed to (i) improving bone marrow hematopoietic microenvironment; (ii) facilitating the cell proliferation and preventing BMNC from apoptosis; (iii) stimulating the expressions of IL-1ß, IL-3, IL-6, SCF and GM-CSF and inhibiting the expression of TGF-ß.

Effect of Colla corii asini (E'jiao) on D-galactose induced aging mice.

Colla corii asini (E'jiao), donkey-hide gelatin prepared by stewing and concentrating from Equus asinus L. donkey hide, is a traditional Chinese medicine preparation widely used in clinical hematic antanemic therapy in China. The aim of the present study was to investigate potential anti-aging effect of Colla corii asini and explore related mechanisms in D-galactose (gal) induced aging model mice. The mice were artificially induced aging by subcutaneously injection with D-gal at the dose of 100 mg/kg·d for 8 weeks. Colla corii asini was simultaneously treated to them once daily by intragastric gavage. Appetite, mental condition, body weight, and organ index were observed. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as levels of malondialdehyde (MDA) in serum, brain, and liver were determined by according assay kits. Western blotting analysis was used to detect p16 and p21 expression. Results indicated that Colla corii asini could improve appetite, mental condition, body weight, and organ condition of model mice, improve SOD, CAT, and GSH-Px activities, reduce MDA levels, and modulate age-related genes expression in D-gal induced mice. Therefore, Colla corii asini may have effect to suppress the aging process through enhancing antioxidant activity, scavenging free radicals, and modulating aging-related gene expression.