Natural products for the treatment of chemotherapy-related cognitive impairment and prospects of nose-to-brain drug delivery.

Chemotherapy-related cognitive deficits (CRCI) as one of the common adverse drug reactions during chemotherapy that manifest as memory, attention, and executive function impairments. However, there are still no effective pharmacological therapies for the treatment of CRCI. Natural compounds have always inspired drug development and numerous natural products have shown potential therapeutic effects on CRCI. Nevertheless, improving the brain targeting of natural compounds in the treatment of CRCI is still a problem to be overcome at present and in the future. Accumulated evidence shows that nose-to-brain drug delivery may be an excellent carrier for natural compounds. Therefore, we reviewed natural products with potential anti-CRCI, focusing on the signaling pathway of these drugs' anti-CRCI effects, as well as the possibility and prospect of treating CRCI with natural compounds based on nose-to-brain drug delivery in the future. In conclusion, this review provides new insights to further explore natural products in the treatment of CRCI.

Ursodeoxycholic acid alleviates sepsis-induced lung injury by blocking PANoptosis via STING pathway.

Acute lung injury (ALI), a progressive lung disease mostly caused by sepsis, is characterized by uncontrolled inflammatory responses, increased oxidative stress, pulmonary barrier dysfunction, and pulmonary edema. Ursodeoxycholic acid (UDCA) is a natural bile acid with various pharmacological properties and is extensively utilized in clinical settings for the management of hepatobiliary ailments. Nonetheless, the potential protective effects and mechanism of UDCA on sepsis-induced lung injuries remain unknown. In this study, we reported that UDCA effectively inhibited pulmonary edema, inflammatory cell infiltration, pro-inflammatory cytokines production, and oxidative stress. Furthermore, UDCA treatment significantly alleviated the damage of pulmonary barrier and enhanced alveolar fluid clearance. Importantly, UDCA treatment potently suppressed PANoptosis-like cell death which is demonstrated by the block of apoptosis, pyroptosis, and necroptosis. Mechanistically, UDCA treatment prominently inhibited STING pathway. And the consequential loss of STING substantially impaired the beneficial effects of UDCA treatment on the inflammatory response, pulmonary barrier, and PANoptosis. These results indicate that STING plays a pivotal role in the UDCA treatment against sepsis-induced lung injury. Collectively, our findings show that UDCA treatment can ameliorate sepsis-induced lung injury and verified a previously unrecognized mechanism by which UDCA alleviated sepsis-induced lung injury through blocking PANoptosis-like cell death via STING pathway.

Zinc supplementation ameliorates sorafenib-induced cognitive impairment through ROS/JNK signaling pathway.

Sorafenib, a multiple kinase inhibitor, is widely used in cancer patients. Recently, clinical studies highlighted the relationship between cognitive deficits and sorafenib exposure. Zinc abundant in the body has been reported to exert neuroprotective activities. However, the effects of zinc supplementation on sorafenib-induced cognitive impairment are still unknown. In the current study, we verified that mice challenged with sorafenib displayed characteristic features of cognitive impairment. However, zinc treatment effectively improved these changes. Histopathological staining also showed that zinc significantly alleviated hippocampal microstructural and ultrastructural damages induced by sorafenib. Meanwhile, zinc significantly reduced sorafenib-induced ROS production and neuronal cells apoptosis in vivo and vitro. Additionally, we also investigated whether zinc protected against sorafenib-induced neuronal cells apoptosis via ROS/JNK pathway through treating SH-SY5Y cells with the NAC or the specific JNK activator anisomycin. The results indicated that NAC performed the same protective effects as zinc in sorafenib-challenged SH-SY5Y cells and activation of JNK by anisomycin partly abolished the protective effects of zinc. Collectively, the present study suggested that inhibition of oxidative stress and the JNK pathway might contribute to the protective effects of zinc against sorafenib-caused cognitive impairment in vivo and vitro.

Mitochondrial Quality Control in Sarcopenia: Updated Overview of Mechanisms and Interventions.

Sarcopenia is a common geriatric disorder characterized by decreased muscle strength, low muscle mass and poor physical performance. This aging-related skeletal muscle deterioration leads to adverse outcomes and severely impairs the quality of life of patients. The accumulation of dysfunctional mitochondria with aging is an important factor in the occurrence and progression of sarcopenia. Mitochondrial quality control (MQC) fundamentally ensures the normal mitochondrial functions and is comprised of four main parts: proteostasis, biogenesis, dynamics and autophagy. Therefore, any pathophysiologic factors compromising the quality control of homeostasis in the skeletal muscle may lead to sarcopenia. However, the specific theoretical aspects of these processes have not been fully elucidated. Current therapeutic interventions using nutritional and pharmaceutical treatments show a modest therapeutic efficacy; however, only physical exercise is recommended as the first-line therapy for sarcopenia, which can ameliorate skeletal muscle deficiency by maintaining the homeostatic MQC. In this review, we summarized the known mechanisms that contribute to the pathogenesis of sarcopenia by impairing normal mitochondrial functions and described potential interventions that mitigate sarcopenia through improving MQC.

Tanreqing Inhibits LPS-Induced Acute Lung Injury In Vivo and In Vitro Through Downregulating STING Signaling Pathway.

Acute lung injury (ALI) is a common life-threatening lung disease, which is mostly associated with severe inflammatory responses and oxidative stress. Tanreqing injection (TRQ), a Chinese patent medicine, is clinically used for respiratory-related diseases. However, the effects and action mechanism of TRQ on ALI are still unclear. Recently, STING as a cytoplasmic DNA sensor has been found to be related to the progress of ALI. Here, we showed that TRQ significantly inhibited LPS-induced lung histological change, lung edema, and inflammatory cell infiltration. Moreover, TRQ markedly reduced inflammatory mediators release (TNF-α, IL-6, IL-1ß, and IFN-ß). Furthermore, TRQ also alleviated oxidative stress, manifested by increased SOD and GSH activities and decreased 4-HNE, MDA, LDH, and ROS activities. In addition, we further found that TRQ significantly prevented cGAS, STING, P-TBK, P-P65, P-IRF3, and P-IκBα expression in ALI mice. And we also confirmed that TRQ could inhibit mtDNA release and suppress signaling pathway mediated by STING in vitro. Importantly, the addition of STING agonist DMXAA dramatically abolished the protective effects of TRQ. Taken together, this study indicated that TRQ alleviated LPS-induced ALI and inhibited inflammatory responses and oxidative stress through STING signaling pathway.

Altered topographical organization of grey matter structural network in early-onset schizophrenia.

Schizophrenia is characterized by both disrupted neurodevelopmental processes and abnormal brain connectivity. However, few studies have examined the atypical features of brain network topography associated with schizophrenia during childhood and adolescence. We used graph theory to compare the grey matter structural networks of individuals (aged 10-15 years) with early-onset schizophrenia (EOS) (n = 25) and a typically-developing (TD) comparison group (n = 31). Compared with the TD group, EOS patients showed significantly increased clustering and local efficiency across a range of network densities (0.3 - 0.4). The network of EOS patients also had more modules (6 modules in EOS vs. 3 modules in controls), indicating a more segregated network at the cost of functional integration. Although our results were preliminary and failed to survive corrections for multiple comparisons, EOS patients might be characterized by altered nodal centrality in several higher-order associative regions including the prefrontal cortex, the hippocampus and the cerebellum. The EOS structural network also lacked the typical left-hemispheric-dominant hub distribution compared with the TD group. These findings suggest that brain structural network was not only globally but also regionally altered in EOS patients.

The effects of posterior cruciate ligament rupture on the biomechanical and histological characteristics of the medial collateral ligament: an animal study.

BACKGROUND: To investigate the effect of complete rupture of the posterior cruciate ligament (PCL) on the biomechanics and histology of the medial collateral ligament (MCL). MATERIALS AND METHODS: Seventy-two male rabbits were randomly divided into two groups: the ruptured group was treated with complete PCL amputation, while the intact group was only subjected to PCL exposure without amputation. Eighteen rabbits were randomly sacrificed at 8, 16, 24, and 40 weeks after the operation, and their specimens were processed for mechanical tensile testing, nano-indentation experiments, hematoxylin-eosin (HE) staining, and picrosirius-polarization staining. RESULTS: There was no significant difference in the length and maximum displacement of the MCL between the ruptured group and the intact group at each time point. The maximum load of the ruptured group was significantly smaller than that of the intact group at 40 W. The elastic modulus and micro-hardness of the ruptured group increased significantly at 24 W and decreased significantly at 40 W. At 16 W and 24 W after PCL rupture, the number of type I collagen fibers and type III collagen fibers in the MCL of the ruptured group was significantly increased compared with that of the intact group. While the type I collagen fibers of the ruptured group were significantly decreased compared with the intact group at 40 W, there was no significant difference in type III collagen fibers between the ruptured group and the intact group. CONCLUSION: PCL rupture has no significant effect on the mechanical and histological properties of MCL in a short period of time under physiological loading, but the histological and mechanical properties of MCL decrease with time.

[Research progress on active components and mechanism of Isatidis Radix for influenza virus].

Isatidis Radix is the dried root of the Isatis indigotica, with pharmacological effects such as heat-clearing and detoxification, cooling blood and pharyngeal relief, antibacterial and anti-inflammatory effects. It is often used clinically to prevent and treat influenza and other diseases. In this paper, relevant domestic and foreign literatures in recent years were summarized, and it was found that Isatidis Radix lignans, indole alkaloids, polysaccharides, etc. were the main active components against influenza virus. Then its pharmacological effects and the mechanism of action were reviewed, providing a basis for in-depth research on the antiviral effect of Isatidis Radix.

circSLC8A1 sponges miR-671 to regulate breast cancer tumorigenesis via PTEN/PI3k/Akt pathway.

Breast cancer is the most frequently diagnosed and the leading cause of cancer-related deaths in women worldwide. However, the role of circSLC8A1 in breast cancer remains elusive. Herein, a cohort of 77 breast tumors and paired adjacent normal mammary tissues were collected. We demonstrated that circSLC8A1 was significantly down-regulated in breast cancer tissues and cell lines, of which expression was negatively correlated with clinical severity and dismal prognosis. Overexpression of circSLC8A1 suppressed cell proliferation, migration and invasion in vitro, and inhibited tumor growth in vivo. CircSLC8A1 directly targeted miR-671 to execute tumor suppressive activities via regulating PI3k/Akt signaling. Krüppel-like factor 16 (KLF16), a transcriptional activator of PTEN, was identified as a target of miR-671. Furthermore, circSLC8A1 could sponge miR-671 to suppress breast tumor growth via PTEN/PI3k/Akt signaling in vivo. In summary, circSLC8A1/miR-671 regulates breast cancer progression through PTEN/PI3k/Akt signaling, which may provide efficient therapeutic target for this devastating cancer.

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms.

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) as common life-threatening lung diseases with high mortality rates are mostly associated with acute and severe inflammation in lungs. With increasing in-depth studies of ALI/ARDS, significant breakthroughs have been made, however, there are still no effective pharmacological therapies for treatment of ALI/ARDS. Especially, the novel coronavirus pneumonia (COVID-19) is ravaging the globe, and causes severe respiratory distress syndrome. Therefore, developing new drugs for therapy of ALI/ARDS is in great demand, which might also be helpful for treatment of COVID-19. Natural compounds have always inspired drug development, and numerous natural products have shown potential therapeutic effects on ALI/ARDS. Therefore, this review focuses on the potential therapeutic effects of natural compounds on ALI and the underlying mechanisms. Overall, the review discusses 159 compounds and summarizes more than 400 references to present the protective effects of natural compounds against ALI and the underlying mechanism.

Possible sarcopenia: early screening and intervention-narrative review.

Sarcopenia is a new geriatric syndrome that has become a heavily researched topic, and it is a potential risk factor for weakness, disability, and death in elderly people. As the world's population ages, the incidence of sarcopenia has also increased, which has resulted in a series of health problems and in large medical costs. Although there are generally accepted diagnostic criteria for sarcopenia, the existing criteria require a comprehensive evaluation of muscle quality, muscle strength and muscle function. Most of these evaluations are time-consuming, labourious, difficult to implement, and unsuitable for large-scale population surveys. Moreover, the abilities of the elderly to undertake daily-life activities are often affected when they are diagnosed with sarcopenia. Therefore, if individuals who are likely to suffer from sarcopenia could be identified by screening at an early stage and then comprehensively evaluated, time and labour would be saved, and the detection rate would be improved. Timely intervention can be undertaken in possible sarcopenia to prevent further development of sarcopenia and strongly improve the quality of life of individuals. This study reviews the early screening and intervention of the possible sarcopenia, analyses its advantages and disadvantages and attempt to identify reliable and practical methods to reduce adverse consequences and the extent of harm.

Altered empathy-related resting-state functional connectivity in adolescents with early-onset schizophrenia and autism spectrum disorders.

Empathy refers to the ability to understand other people's feelings and reacting emotionally to others. Impaired empathy has been reported in both individuals with schizophrenia and autism spectrum disorders (ASD). Despite overlaps, few studies have directly examined the neural mechanisms of impaired empathy in these two clinical groups. We used resting-state fMRI to investigate the neural correlates of empathic functioning in adolescents with ASD (N = 11), early-onset schizophrenia (EOS) (N = 20), and typically developing (TD) controls (N = 26). Their parents completed the Griffith Empathy Measure (GEM) to assess the adolescents' empathic capacity. We found that EOS and ASD participants both exhibited impaired empathy as measured by the GEM, especially in cognitive empathy (post-hoc ps < 0.05). Regions-of-interest-based functional connectivity revealed decreased connectivity between the salience network (SN) (i.e., the anterior insula and the anterior cingulate cortex) and core regions of the mentalizing network (e.g., the temporal-parietal junction and the precuneus), and among the SN and the bilateral superior temporal gyri (STG) and the left cerebellum in EOS participants. Subsequent comparisons revealed reduced grey matter volume in the STG bilaterally in both clinical groups. Increased resting-state functional connectivity within the social brain network was correlated with higher parent-reported scores of empathic capacity in TD adolescents, but such a brain-phenotype relationship was absent in the two clinical groups. These findings indicate that structural alterations and disturbed resting-state functional connectivity in the core empathy network may be the neural correlates of social cognitive deficits in individuals with EOS and ASD.

Iridoid glycosides from Morinda officinalis How. exert anti-inflammatory and anti-arthritic effects through inactivating MAPK and NF-κB signaling pathways.

BACKGROUND: The root of Morinda officinalis How. (MO, the family of Rubiaceae) has long been used to treat inflammatory diseases in China and other eastern Asian countries, and iridoid glycosides extracted from MO (MOIG) are believed to contribute to this anti-inflammatory effect. However, the mechanism underlying the anti-inflammatory and anti-arthritic activities of MOIG has not been elucidated. The aim of the present study was to determine how MOIG exerted anti-inflammatory and anti-arthritic effects in vivo and in RAW 264.7 macrophages. METHODS: MOIG were enriched by XDA-1 macroporous resin. The maximum feasible dose method was adopted to evaluate its acute toxicity. The analgesic effect of MOIG was evaluated by acetic acid writhing test and the anti-inflammatory effect was evaluated by cotton-pellet granuloma test in rats and air pouch granuloma test in mice. The anti-arthritic effect was evaluated by establishing an adjuvant arthritis model induced by Complete Freund's Adjuvant (CFA). The viability of the cultured RAW 264.7 macrophages was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The anti-inflammatory activity was evaluated by measuring NO, IL-1ß, IL-6 and TNF-α levels in LPS-stimulated RAW 264.7 cells. The protein level of inflammatory responsive genes was evaluated by Western blot analysis. RESULTS: MOIG had no significant toxicity at maximum feasible dose of 22.5 g/kg. MO extracts and MOIG (50,100 and 200 mg/kg) all evoked a significantly inhibitory effects on the frequency of twisting induced by acetic acid in mice compared with the model control group. Administration of MO extracts and MOIG markedly decreased the dry and wet weight of cotton pellet granuloma in rats and air pouch granuloma in mice. MOIG significantly attenuated the paw swelling and decreased the arthritic score, weight loss, spleen index, and the serum level of inflammatory factors IL-1ß, IL-6 and IL-17a in CFA-induced arthritic rats. MOIG inhibited the production of inflammatory cytokines in LPS-stimulated RAW264.7 cells, and the expressions of iNOS, COX-2 and proteins related to MAPK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 macrophages. CONCLUSION: MOIG exerted anti-inflammatory and anti-arthritic activities through inactivating MAPK and NF-κB signaling pathways, and this finding may provide a sound experimental basis for the clinical treatment of rheumatoid arthritis with MOIG.

Sex differences in the effects of lead exposure on growth and development in young children.

The adverse effects of lead exposure on children's health have been widely investigated. Physical growth is a central indicator of health in early childhood. However, studies on the associations between lead exposure and the physical growth of young children are still equivocal. This study aimed to investigate the effects of lead exposure on young children's growth. A cross-sectional survey was conducted, and a total of 1678 young children were recruited. Blood lead levels were determined by graphite furnace atomic absorption spectrophotometry and anthropometric measurements were obtained by nurses. The weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ) and BMI for-age Z-score (BMIZ) of the children were calculated according to World Health Organization standards. Multivariable linear models after adjustment for potential confounders were used to evaluate the associations between lead exposure and childhood anthropometric characteristics. Meanwhile, the sex differences in these associations were also examined. The median blood lead levels in total subjects, in boys and in girls were 46.44, 49.00 and 43.27 µg/L, respectively. After adjusting for confounders, a significantly negative association of blood lead levels with WAZ and HAZ was observed. After stratification by sex, the blood lead levels in children were negatively associated with WAZ and HAZ in boys but not in girls. Meanwhile, we further provide evidence that blood lead levels below 50 µg/L may also have adverse effects on young children's HAZ. Our findings suggest that lead exposure may have sex-specific effects on physical growth in young children and that blood lead level in a low levels may also have adverse effects on children's physical growth and development.

Differential profiles of response inhibition deficit between male children with autism spectrum disorders and schizophrenia.

Autism spectrum disorders (ASD) and schizophrenia (SZ) are both associated with response inhibition impairment. However, the relative pattern of deficits in these two disorders remains unclear. Twenty-three male children with ASD, 23 male children with SZ, and 32 typically developing male controls were recruited to complete a set of tasks measuring response inhibition in the visual, auditory, and verbal domains. We found that visual, auditory, and verbal response inhibitions were impaired in both children with ASD and children with SZ. Compared with typically developing controls, children with ASD made more commission errors whereas children with SZ responded much slower in the visual response inhibition task. Both clinical groups showed comparable impairment in verbal response inhibition, but children with SZ were more impaired in auditory response inhibition than children with ASD. These different patterns of response inhibition deficit between male children with ASD and SZ may help to differentiate between these two disorders and may be potential targets for intervention. Autism Res 2020, 13: 591-602. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this study, we found that male children with autism spectrum disorder (ASD) made more commission errors whereas male children with schizophrenia (SZ) responded much slower in the visual response inhibition task. Both clinical groups exhibited comparable impairments in verbal response inhibition, but male children with SZ were more impaired in auditory response inhibition than male children with ASD. Our findings provide potential targets for intervention.

Phenylethanoid glycosides from the Schnabelia nepetifolia (Benth.) P.D.Cantino promote the proliferation of osteoblasts.

An investigation of the n-BuOH fraction of Schnabelia nepetifolia (Benth.) P.D.Cantino led to the isolation and identification of 12 undescribed phenylethanoid glycosides (nepetifosides A-L) and one undescribed phenylmethanoid glycoside (nepetifoside M), together with 23 known compounds. The structures of these compounds were determined by spectroscopic analyses including two-dimensional nuclear-magnetic-resonance (2D-NMR) spectroscopy and chemical-hydrolysis methods. Nepetifoside F exhibited strong activity that significantly increased osteoblast proliferation at three concentrations of 0.1, 1, and 10 µM. Moreover, nepetifoside C and nepetifoside D exhibited moderate activities in promoting the proliferation of osteoblasts at medium and high concentrations of 1 µM and 10 µM, respectively.

Effects of lead, mercury, aluminium and manganese co-exposure on the serum BDNF concentration of pre-school children in Taizhou, China.

Previous studies have shown that toxic metal exposure can have adverse effects on the nervous system of children, but the toxicology of metal co-exposure on neurodevelopment remains to be clarified. Brain derived neurotrophic factor (BDNF) plays an important role in nervous system development, but the possible effects of metal co-exposure on the serum BDNF concentrations of children remain unknown. A total of 561 children living in Taizhou City, China were recruited to participate in our cross-sectional multicenter survey. We measured their blood Pb, Hg, Al and Mn levels and serum BDNF concentrations as well as determined their associations in the total and within sex subgroups. The geometric means of the blood Pb, Hg, Al and Mn levels in all the participants were 67.18 µg/L, 1.01 µg/L, 52.03 µg/L and 18.26 µg/L, respectively. The serum BDNF concentration in children was 19.45 ng/mL. After adjusting for confounders, the blood Pb levels were significantly negatively associated with the serum BDNF concentrations in all the subjects and boys but not in girls. In addition, a significantly negative interaction between blood Pb and blood Hg and a positive interaction between blood Pb and blood Al on serum BDNF concentrations were also observed in boys but not in girls. Our findings highlight the toxic effects of metal co-exposure on serum BDNF levels in pre-school children and indicate that these effects might differ by gender, which suggest that special attention should be paid to the sex-specific effects of metal exposure.

Rubiadin-1-methyl ether from Morinda officinalis How. Inhibits osteoclastogenesis through blocking RANKL-induced NF-κB pathway.

Rubiadin-1-methyl ether (RBM) is a natural anthraquinone compound isolated from the root of Morinda officinalis How. In our previous study, RBM was found to have inhibitory effects on the TRAP activity of osteoclasts, which means that RBM may be a candidate for therapy of bone diseases characterized by enhanced bone resorption. However, the further effect of RBM on osteoclasts and the underlying mechanism remain unclear. In the present study, we investigated the effects of RBM isolated from Morinda officinalis How. on osteoclasts derived from bone marrow macrophages (BMMs) and the underlying mechanism in vitro. RBM at the dose that did not affect the viability of cells significantly inhibited RANKL-induced osteoclastogenesis and actin ring formation of osteoclast, while RBM performed a stronger effect at the early stage. In addition, RBM downregulated the expression of osteoclast-related proteins, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cellular oncogene Fos (c-Fos), matrix metallopeptidase 9 (MMP-9) and cathepsin K (CtsK) as shown by Western blot. Furthermore, RBM inhibited the phosphorylation of NF-κB p65 and the degradation of IκBα as well as decreased the nuclear translocation of p65. Collectively, the results suggest that RBM inhibit osteoclastic bone resorption through blocking NF-κB pathway and may be a promising agent for the prevention and treatment of bone diseases characterized by excessive bone resorption.

Pharmacokinetics and tissue distribution of monotropein and deacetyl asperulosidic acid after oral administration of extracts from Morinda officinalis root in rats.

BACKGROUND: Iridoid glycosides (IGs), including monotropein (MON) and deacetyl asperulosidic acid (DA) as the main ingredients, are the major chemical components in Morinda officinalis How. (MO) root, possessing various pharmacological properties including anti-osteoporosis, anti-inflammation and anti-rheumatism activities.The aim of the present study was to further elucidate the pharmacological actions of MO by investigating the pharmacokinetics and tissue distribution of IGs in MO. METHODS: An ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) method was developed and validated for simultaneous determination of MON and DA levels in plasma and various tissues of Wistar rats. MON, DA and acetaminophen (ACE) as the internal standard (IS) were extracted from rat plasma and tissue samples by direct deproteinization with methanol. The rats were administered orally at 1650 mg/kg MO and 25, 50 and 100 mg/kg MO iridoid glycosides (MOIGs) or intravenously at MOIG 25 mg/kg for pharmacokinetic study of MON and DA. In addition, 100 mg/kg MOIG was administered orally for tissue distribution study of MON and DA. Non-compartmental pharmacokinetic profiles were constructed. Tissue distributions were calculated according to the validated methods. RESULTS: Significant differences in the pharmacokinetic parameters were observed in male and female rats. The AUC0-t, Cmax and bioavailability of MON and DA in female rats were higher than those in male rats. MON and DA mainly distributed in the intestine and stomach after oral administration, and noteworthily high concentrations of MON and DA were detected in the rat hypothalamus. CONCLUSION: The results of the present study may shed new lights on the biological behavior of MOIGs in vivo, help explain their pharmacological actions, and provide experimental clues for rational clinical use of these IGs extracted from the MO root.

The prevalence of psychiatric disorders among students aged 6~ 16 years old in central Hunan, China.

BACKGROUND: Though several epidemiological surveys of psychiatric disorders have been carried out in China, only a few of them are concerned about the prevalence of psychiatric disorders in central Hunan and reveal the distribution of common psychiatric disorders and their comorbidities. METHODS: Achenbach's Child Behavior Checklist (CBCL), the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID), and Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) were administered to a stratified sample of 17,071 participants aged 6 to 16 years old from two cities in the central part of Hunan province. Twelve-month prevalence rates were calculated. RESULTS: Twelve-month prevalence of the population was 9.74%. The most common psychiatric disorders were attention deficit hyperactivity disorder (ADHD) (4.96%), oppositional defiant disorder (ODD) (2.98%) and generalized anxiety disorder (GAD) (1.77%). Of those with a 12-month prevalence diagnosis, 34.6% had one or more comorbid psychiatric disorders. Most notably, ADHD had comorbidity rates of 25.15% with ODD, 18.18% with CD, 6.38% with GAD, and 3.66% with MDD. CONCLUSIONS: Psychiatric disorders are common in Chinese children and adolescents. Being the most prevalent mental disorder, ADHD requires continued focus and support in awareness and education.