Shinn-Zong Lin

Homozygous deletion genotype of angiotensin converting enzyme confers protection against migraine in man.

Studies have shown that migraine may have a major genetic component. Meanwhile, angiotensin converting enzyme (ACE) gene has been implicated as a genetic factor associated with migraine. We designed a case-control study to investigate the association between ACE and migraine in 240 migraine patients and 200 healthy controls, matched by age and sex. There was no significant difference in allelic frequency (I and D) and genotype polymorphism (DD, DI and II) of the ACE gene in migraine patients and controls. Analysis of the difference in ACE polymorphism stratified by gender revealed that male migraine patients with the homozygote DD genotype (ACE-DD) were significantly fewer than that of male controls (OR = 0.331, p = 0.045). There was no existence of a difference among the frequency and duration of headache in each subgroup of migraine patients stratified by ACE genotype. Our findings indicate that ACE-DD may have a slight protective effect against migraine in male patients.

n-Butylidenephthalide exhibits protection against neurotoxicity through regulation of tryptophan 2, 3 dioxygenase in spinocerebellar ataxia type 3

&NA; Spinocerebellar ataxia type 3 or Machado‐Joseph disease (SCA3/MJD) is characterized by the repetition of a CAG codon in the ataxin‐3 gene (ATXN3), which leads to the formation of an elongated mutant ATXN3 protein that can neither be denatured nor undergo proteolysis in the normal manner. This abnormal proteolysis leads to the accumulation of cleaved fragments, which have been identified as toxic and further they act as a seed for more aggregate formation, thereby increasing toxicity in neuronal cells. To date, there have been few studies or treatment strategies that have focused on controlling toxic fragment formation. The aim of this study is to develop a potential treatment strategy for addressing the complications of toxic fragment formation and to provide an alternative treatment strategy for SCA3. Our preliminary data on anti‐aggregation and toxic fragment formation using an HEK (human embryonic kidney cells) 293T‐84Q‐eGFP (green fluorescent protein) cell model identified n‐butylidenephthalide (n‐BP) as a potential drug treatment for SCA3. n‐BP decreased toxic fragment formation in both SCA3 cell and animal models. Moreover, results showed that n‐BP can improve gait, motor coordination, and activity in SCA3 mice. To comprehend the molecular basis behind the control of toxic fragment formation, we used microarray analysis to identify tryptophan metabolism as a major player in controlling the fate of mutant ATXN3 aggregates. We also demonstrated that n‐BP functions by regulating the early part of the kynurenine pathway through the downregulation of tryptophan 2, 3‐dioxygenase (TDO2), which decreases the downstream neurotoxic product, quinolinic acid (QA). In addition, through the control of TDO2, n‐BP also decreases active calpain levels, an important enzyme involved in the proteolysis of mutant ATXN3, thereby decreasing toxic fragment formation and associated neurotoxicity. Collectively, these findings indicate a correlation between n‐BP, TDO2, QA, calpain, and toxic fragment formation. Thus, this study contributes to a better understanding of the molecular interactions involved in SCA3, and provides a novel potential treatment strategy for this neurodegenerative disease. Graphical abstract Figure. No caption available. Highlightsn‐BP has anti‐aggregating and pro‐proliferative effect which aid in improvement of the pathological state of SCA3 mice.In SCA3, TDO2 has been observed to be upregulated which in turn upregulates downstream product QA.QA being an agonist of NMDA‐R further may increase the influx of Ca2+ ions which increases Ca 2+ dependent calpain activity.Calpain through proteolysis cleaves mutant ATXN3 to form toxic fragment.Hence, n‐BP may decrease toxic fragment formation through its activity on TDO2 and improve the SCA3 neuropathology.

Effect of Cinnamomum osmophloeum Kanehira Leaf Aqueous Extract on Dermal Papilla Cell Proliferation and Hair Growth

In this study, we explored the effect of the water extract of Cinnamomum osmophloeum Kanehira (COK) leaves on hair growth by in vitro and in vivo assays. Using an in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, it was found that the proliferation of rat vibrissae and human hair dermal papilla cells (hDPCs) was significantly enhanced by the COK leaf extract treatment. As determined by quantitative real-time polymerase chain reaction (RT-PCR), the messenger RNA (mRNA) levels of some hair growth–related factors including vascular endothelial growth factor, keratinocyte growth factor (KGF), and transforming growth factor-β2 were found to be higher in the cultured hDPCs exposed to COK leaf extract than those in the untreated control group. In the hair-depilated C57BL/6 mouse model, the stimulation of hair growth was demonstrated in the group of COK leaf extract treatment. Both photographical and histological observations revealed the promotion of the anagen phase in the hair growth cycle by the COK leaf extract in the C57BL/6 mice. Finally, the ultra performance liquid chromatography (UPLC) showed that the COK extract contained mostly cinnamic aldehyde and a small amount of cinnamic acid. The results suggest that the COK leaf extract may find use for the treatment of hair loss.

Adipose-derived Stem Cells Stimulated with n-Butylidenephthalide Exhibit Therapeutic Effects in a Mouse Model of Parkinson’s Disease

Parkinson’s disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages. However, treatment of PD using adult stem cells is known to be less efficacious than neuron or embryonic stem cell transplantation. Therefore, improved therapies are urgently needed. n-Butylidenephthalide (BP), which is extracted from Angelica sinensis, has been shown to have anti-inflammatory and neuroprotective effects. Indeed, we previously demonstrated that BP treatment of ADSCs enhances the expression of neurogenesis and homing factors such as nuclear receptor related 1 protein, stromal-derived factor 1, and brain-derived neurotrophic factor. In the present study, we examined the ability of BP-pretreated ADSC transplantation to improve PD motor symptoms and protect dopamine neurons in a mouse model of PD. We evaluated the results using neuronal behavior tests such as beam walking, rotarod, and locomotor activity tests. ADSCs with or without BP pretreatment were transplanted into the striatum. Our findings demonstrated that ADSC transplantation improved motor abilities with varied efficacies and that BP stimulation improved the therapeutic effects of transplantation. Dopaminergic cell numbers returned to normal in ADSC-transplanted mice after 22 d. In summary, stimulating ADSCs with BP improved PD recovery efficiency. Thus, our results provide important new strategies to improve stem cell therapies for neurodegenerative diseases in future studies.

Effects of Moxibustion on the Levels of Insulin-Like Growth Factor 1: A Pilot Study

Moxibustion (艾灸) is a traditional Chinese medicine therapy performed using Artemisia argyii. Zusanli (足三里, ST36) is an acupoint in the stomach meridian, long associated in ancient Chinese medical practices with the extension of life span when moxibustion is applied to it. The aim of this study was to investigate changes in insulin-like growth factor 1 (IGF-1) levels after application of moxibustion to ST36. Four healthy men and women participated in this 28-day trial and were randomly divided into 2 groups. Group A received moxibustion treatment from days 1 to 14, while group B received moxibustion treatment from days 15 to 28. Blood samples were taken 5 times during this study to measure serum IGF-1 (s-IGF-1) levels. The s-IGF-1 levels increased in both groups after 7 and 14 d of moxibustion therapy (group A: 11.02% [7 d] and 29.65% [14 d]; group B: 169.12% [7 d] and 274.85% [14 d]). After moxibustion therapy had been completed (day 14), s-IGF-1 levels continued to increase in group A (increases on day 21 and day 28 were 53.19% and 61.45%, respectively). There were no adverse events in either group. The s-IGF-1 levels were significantly raised in both groups after 7 and 14 d of moxibustion therapy. Moreover, once therapy had been completed, s-IGF-1 levels continued to increase in group A up to 14 d after the treatment.

A PEG-Based Hydrogel for Effective Wound Care Management

It is extremely challenging to achieve strong adhesion in soft tissues while minimizing toxicity, tissue damage, and other side effects caused by wound sealing materials. In this study, flexible synthetic hydrogel sealants were prepared based on polyethylene glycol (PEG) materials. PEG is a synthetic material that is nontoxic and inert and, thus, suitable for use in medical products. We evaluated the in vitro biocompatibility tests of the dressings to assess cytotoxicity and irritation, sensitization, pyrogen toxicity, and systemic toxicity following the International Organization for Standardization 10993 standards and the in vivo effects of the hydrogel samples using Coloskin liquid bandages as control samples for potential in wound closure.