Thalamic gray matter volume mediates the association between KIBRA polymorphism and olfactory function among older adults: a population-based study.

The kidney and brain expressed protein (KIBRA) rs17070145 polymorphism is associated with both structure and activation of the olfactory cortex. However, no studies have thus far examined whether KIBRA can be linked with olfactory function and whether brain structure plays any role in the association. We addressed these questions in a population-based cross-sectional study among rural-dwelling older adults. This study included 1087 participants derived from the Multidomain Interventions to Delay Dementia and Disability in Rural China, who underwent the brain MRI scans in August 2018 to October 2020; of these, 1016 took the 16-item Sniffin' Sticks identification test and 634 (62.40%) were defined with olfactory impairment (OI). Data were analyzed using the voxel-based morphometry analysis and general linear, logistic, and structural equation models. The KIBRA rs17070145 C-allele (CC or CT vs. TT genotype) was significantly associated with greater gray matter volume (GMV) mainly in the bilateral orbitofrontal cortex and left thalamus (P < 0.05) and with the multi-adjusted odds ratio of 0.73 (95% confidence interval 0.56-0.95) for OI. The left thalamic GMV could mediate 8.08% of the KIBRA-olfaction association (P < 0.05). These data suggest that the KIBRA rs17070145 C-allele is associated with a reduced likelihood of OI among older adults, partly mediated through left thalamic GMV.

Use of Cardiovascular Drugs for Primary and Secondary Prevention of Cardiovascular Disease Among Rural-Dwelling Older Chinese Adults.

Cardiovascular risk factors and related disorders are common among older adults, and use of various classes of cardiovascular (CV) drugs could reduce the risk of cardiovascular disease (CVD). However, data are sparse with regard to the use of CV drugs among rural-dwelling older adults in China. Therefore, this population-based study aimed to describe use of CV drugs among older adults living in the rural communities in China, while taking into account the use of CV drugs for primary and secondary prevention of CVDs. This study included 5,246 participants (age ≥65 years; 57.17% women; 40.68% illiteracy) in the baseline examination of the MIND-China study. In March-September 2018, data on health-related factors, CVDs (ischemic heart disease, atrial fibrillation, heart failure, and stroke), and CV drug use were collected via face-to-face survey, clinical examination, and laboratory tests. We classified CV drugs according to the Anatomical Therapeutic Chemical classification system for western medications and specific cardiovascular effects for the products of traditional Chinese medicine (TCM). We conducted descriptive analysis. The overall prevalence of major cardiovascular risk factors ranged from 14.30% in diabetes and 23.81% in dyslipidemia to 66.70% in hypertension, and CVDs affected 35.07% of all participants (36.28% in women vs. 33.47% in men, p = 0.035). In the total sample, calcium channel blockers (C08) were most commonly used (10.39%), followed by TCM products (7.64%), hypoglycemic agents (A10, 4.73%), renin-angiotensin system (RAS)-acting agents (C09, 4.61%), and lipid-lowering agents (C10, 4.17%). The proportions of CV drugs for primary prevention (i.e., use of CV drugs among people without CVD) were 3.14% for antithrombotic agents (mainly aspirin), 1.38% for lipid-lowering agents, and 3.11% for RAS-acting agents; the corresponding figures for secondary prevention (i.e., use of CV drugs among people with CVD) were 13.97%, 9.35%, and 7.39%. In conclusion, despite highly prevalent cardiovascular risk factors and CVDs, a fairly low proportion of the rural-dwelling older adults take CV medications for primary and secondary prevention. Notably, TCM products are among the most commonly used CV drugs. These results call for additional efforts to promote implementation of the evidence-based recommendations for prevention of CVDs in the primary care settings.

Understanding the Association Between Negative Life Events and Suicidal Risk in College Students: Examining Self-Compassion as a Potential Mediator.

OBJECTIVE: We tested a hypothesized model consistent with the notion that self-compassion mediates the association between negative life events and suicidal risk (viz., depressive symptoms and suicidal behaviors) in college students METHOD: The sample was comprised of 331 college students. Self-compassion facets (viz., self-kindness, self-judgment, common humanity, isolation, mindfulness, and overidentification) were used in testing for multiple mediation, controlling for sex. RESULTS: Common humanity, mindfulness, and overidentification were found to mediate the association between negative life events (NLE) and depressive symptoms. However, common humanity was found to be the only mediator of the association between NLE and suicidal behaviors. CONCLUSION: These findings suggest that there are specific facets of self-compassion that account for the association between NLE and suicidal risk in college students and that (loss of) common humanity plays a central role in this process.

Increased plasma orexin-A levels in patients with insomnia disorder are not associated with prepro-orexin or orexin receptor gene polymorphisms.

Orexins, also known as hypocretins, play a regulatory role in the sleep-wake cycle by activating orexin receptors. Previous animal studies have shown that sleep deprivation can elevate orexinergic peptide levels. However, the relationship between insomnia disorder and orexin-A levels in humans has not been explored. In the current study, we examined plasma orexin-A levels in patients with insomnia disorder and in normal sleepers. We also studied the possible mechanisms underlying changes in orexin-A levels between the study groups; this included investigations of prepro-orexin and orexin receptor gene polymorphisms as well as exploration of other variables. We measured plasma orexin-A levels in 228 patients with insomnia disorder and 282 normal sleepers. The results indicated that the patients with insomnia disorder had significantly higher orexin-A levels than normal sleepers (63.42±37.56 vs. 54.84±23.95pg/ml). A positive relationship was detected between orexin-A level and age in patients with insomnia disorder. Orexin-A levels were elevated in relation to course of insomnia, as well as in relation to increased Insomnia Severity Index score. None of the evaluated prepro-orexin gene single nucleotide polymorphisms were informative between the two study populations. After sequencing all orexin receptor exons, one variation (rs2271933) in the OX1R gene and one variation (rs2653349) in the OX2R gene were found. However, no significant differences were found in either genotypic or allelic frequency distributions between the two study groups. It is suggested that the increased plasma orexin-A levels in patients with insomnia disorder are associated with the course and severity of insomnia, but not with prepro-orexin and orexin receptor gene polymorphisms.

The effect of Scutellaria baicalensis stem-leaf flavonoids on spatial learning and memory in chronic cerebral ischemia-induced vascular dementia of rats.

Flavonoids have been shown to improve cognitive function and delay the dementia progression. However, the underlying mechanisms remain elusive. In the present study, we examined the effect of Scutellaria baicalensis stem-leaf total flavonoids (SSTFs) extracted from S. baicalensis Georgi on spatial learning and memory in a vascular dementia (VaD) rat model and explored its molecular mechanisms. The VaD rats were developed by permanent bilateral occlusion of the common carotid artery. Seven days after recovery, the VaD rats were treated with either 50 or 100 mg/kg of SSTF for 60 days. The spatial learning and memory was evaluated in the Morris water maze (MWM) test. The tau hyperphosphorylation and the levels of the related protein kinases or phosphatases were examined by western blot analysis. In VaD rats, SSTF treatment at 100 mg/kg significantly reduced the escape latency in training trial in MWM test. In the probe trial, SSTF treatment increased the searching time and travel distance in the target quadrant. SSTF treatment inhibited the tau phosphorylation in both cortex and hippocampus in VaD rats. Meanwhile, SSTF reduced the activity of glycogen synthase kinase 3ß and cyclin-dependent kinase 5 in VaD rats. In contrast, SSTF treatment increased the level of the protein phosphatase 2A subunit B in VaD rats. SSTF treatment significantly improved the spatial cognition in VaD rats. Our results suggest that SSTF may alleviate tau-hyperphosphorylation-induced neurotoxicity through coordinating the activity of kinases and phosphatase after a stroke. SSTF may be developed into promising novel therapeutics for VaD.

Dual regulating effect of Ningdong granule on extracellular dopamine content of two kinds of Tourette's syndrome rat models.

Tourette's syndrome (TS) is an inherited chronic neuropsychiatric disorder characterized by involuntary stereotyped motor and phonic behaviors called tics. Its pathogenesis is still unclear and its treatment remains limited. Our previous basic and clinical studies have shown that traditional Chinese medicine (TCM) preparation Ningdong granule (NDG) is effective for the treatment of TS with little side effects. In the current study, two TS rat models (Apomorphine (Apo)- and 3,3'-iminodipropionitrile (IDPN)-induced) were used to explore the dual regulating effects and mechanisms of NDG on extracellular DA concentration. We found that NDG could regulate the extracellular DA concentration dually: it could make a gradual recovery in extracellular DA content from both an up-regulated level in Apo-induced rats and down-regulated level in IDPN-induced rats measured by high-performance liquid chromatography (HPLC). The protein expression of DA transporter (DAT) was measured by Western blot and the result showed that NDG could elevate DAT expression when DA release was up-regulated and could decrease DAT expression when extracellular DA concentration was down-regulated. The main mechanism of the dual regulating effect of NDG on extracellular DA release might be related to DAT protein expression in TS, through which the released DA is re-uptaken into nerve terminals. Taken together, compared with conventional single-target anti-tics drugs such as haloperidol (Hal), NDG with the dual regulating effect would be more significant for TS treatment.

Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus.

Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions.

Increased iron level in motor cortex of amyotrophic lateral sclerosis patients: an in vivo MR study.

Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative disorders, but no definite mechanism has been defined on the loss of motor neurons in ALS and currently no therapy can block its progression. Many lines of evidence indicate that there is a disorder of iron homeostasis in ALS, and thus we sought to test the iron level in ALS patients by susceptibility weighted imaging (SWI). Sixteen ALS patients and 16 healthy persons underwent brain scans using SWI with a 3T Siemens MR scanner. The red nucleus, substantia nigra, globus pallidus, putamen, the head of caudate nucleus, and motor cortex were measured in the filtered phase images and analysed for their SWI phase values as relative marker for iron content. We found that phase shift values were significantly higher in the motor cortex of ALS patients by SWI, indicating increased iron level in this area. In contrast, we found that there were no differences of phase shift values between ALS patients and healthy controls in the other nuclei including the red nucleus, substantia nigra, globus pallidus, putamen and the head of the caudate nucleus. Furthermore, we found that there were no relationships between SWI signal and some clinical features of ALS. In conclusion, these results demonstrate that iron level increases in the motor cortex of ALS and that SWI is a reliable method to test iron in the brain.