Unveiling the anticancer effect of traditional Chinese herbal medicine

In this issue of World Journal of Gastroenterology,Huang et al reported that Calculus bovis(CB),a traditional Chinese herbal medicine,impedes the growth of liver cancers in vivo.Through further in vitro studies,they showed that CB suppressed the M2 polarization of tumor-associated macrophages by suppressing the Wnt signaling pathway,which consequently inhibited the growth of liver cancer.Although the effects of traditional Chinese herbal medicine are often not scientifically proven,Huang et al successfully identified the molecular mechanism involved in the anticancer effect of CB,and it is anticipated that the molecular mechanisms involved in the effects of other traditional Chinese herbal medicines will be scientifically elucidated,as demonstrated in this article.

The Development of a Feeding Coparenting Scale for Japanese Parents of Fifth- and Sixth-Grade Elementary School Children

Aim: Recently, the role of feeding coparenting has gained attention in the child eating research field. The Feeding Coparenting Scale (FCS), a measure of how caregivers interact with their partners when feeding their children was developed in the United States in 2019. However, there is no valid and reliable measure to assess feeding coparenting among caregivers of school-aged children in Japan. Therefore, this study aimed to develop a Japanese version of the FCS (FCS-J) questionnaire for caregivers with school-aged children. Methods: This was a web-based cross-sectional survey completed by caregivers of children aged 10-12 years. A preliminary survey using interviews and a web-based survey was conducted and found that the translated items of the FCS into Japanese were understandable to Japanese people. The developed survey was administered to parents of children at an elementary school. The reliability of the survey was assessed using both test-retest reliability and internal consistency analysis. Exploratory factor analysis was used to test construct validity, and known population validity was examined in relation to attributes, marital satisfaction, and feeding tasks. Results: Findings with 135 parents of school-aged children showed good internal reliability and validity of the FCS-J. The mean score for the overall FCS-J score was 46.2 (SD = 6.2), with Cronbach’s α of 0.72. For the subscales, Cronbach’s α ranged from 0.75 to 0.79. In sum, the present study’s results support the three-factor structure of the FCS in Japanese caregivers in Japan. Conclusions: The developed FCS-J was found to have a certain degree of reliability and validity. In this study, a Japanese version of the FCS-J was developed. .

Therapeutic potential of stem cells in subarachnoid hemorrhage

Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

Comparing role of ATP between acute pain in neuromyelitis optica spectrum disorder and peripheral neuropathic pain

In this article, we present our previous research, which highlighted adenosine triphosphate(ATP) as the cause of neuropathic pain during the acute phase of neuromyelitis optica spectrum disorder(NMOSD). In NMOSD pathology, damageassociated molecular patterns(DAMPs), including ATP, are released from damaged astrocytes, triggering the activation of innate immune cells. ATP is a central mediator of acute pain in NMOSD.

Role of resident memory T cells in neuroinflammatory and neurodegenerative diseases in the central nervous system

The immune system has been attracting increasing attention in the field of chronic neurological disorders in the central nervous system(CNS).Autoreactive T cells targeting CNS antigens play a crucial role in the development of various autoimmune diseases,such as multiple sclerosis(MS)and neuromyelitis optica spectrum disorder(NMOSD).Moreover,T cells are now recognized as a pivotal contributor to the pathology of neurodegenerative disorders,including Alzheimer's disease(AD),Parkinson's disease(PD),and multiple system atrophy.

Roles of N-cadherin in cerebral cortical development:cooperation with membrane trafficking and actin cytoskeletal regulation

Cell adhesion plays pivotal roles in the morphogenesis of multicellular organisms.Epithelial cells form several types of cell-to-cell adhesion,including zonula occludens(tight junctions),zonula adhaerens(adherens junctions),and macula adhaerens(desmosomes).Although these adhesion complexes are basically observed only in epithelial cells,cadherins,which are the major cell adhesion molecules of adherens junctions,are expressed in both epithelial and non-epithelial tissues,including neural tissues(Kawauchi,2012).The cadherin superfamily consists of more than 100 members,but classic cadherins.

Disruption of neuronal actin barrier promotes the entry of disease-implicated proteins to exacerbate amyotrophic lateral sclerosis pathology

Amyotrophic lateral sclerosis(ALS)is a devastating neurological disease characterized by the accumulation of aberrant proteins in motor neurons of the brain and spinal cord.Patients with ALS develop skeletal muscle weakness,resulting in death from respiratory paralysis,which usually occurs 2-4 years after clinical onset(Goutman et al.,2022).

Objective assessment of the antispasmodic effect of Shakuyaku-kanzo-to (TJ-68),a Chinese herbal medicine,on the colonic wall by direct spraying during colonoscopy

AIM： To objectively evaluate the effect of TJ-68 on colonic spasms during colonoscopy. METHODS： One hundred and one patients subjected to screening colonoscopy were randomly assigned to two groups： T1-68 in 51 subjects and saline as the control in 50. The endoscope was inserted into the sigmoid colon, then a spastic region was identified and the tip of the colonoscope was positioned at a distance of about 10 mm from the spastic region. The endoscopic view was recorded before and after direct spraying of the TJ-68 solution or warm saline. The intraluminal area of the spastic region was serially measured using a computer image analyzer and expressed as pixel counts. The area under the curve （AUC） was calculated from the pixel curve. Statistical significance was assessed by Wilcoxon＇s test and Mann-Whitney U test. RESULTS： The mean AUC of the spastic region before and after TJ-68 spraying was 29 128 and 121 943 pixels, respectively, while with saline, it was 31 635 pixels and 48 617 pixels, respectively. Thus, the AUC significantly increased after TL-68 spraying compared with the spraying of saline （P〈0.001）. CONCLUSION： Direct spraying of TJ-68 on the colonic mucosa suppressed colonic spasm and it may be useful during colonoscopy when anticholinergic agents are contraindicated.

Clinical Effects of Hydrogen Administration: From Animal and Human Diseases to Exercise Medicine

Here we review the literature on the effects of molecular hydrogen (H2) on normal human subjects and patients with a variety of diagnoses, such as metabolic, rheumatic, cardiovascular and neurodegenerative and other diseases, infections and physical and radiation damage as well as effects on aging and exercise. Although the effects of H2 have been studied in multiple animal models of human disease, such studies will not be reviewed in depth here. H2 can be administered as a gas, in saline implants or infusions, as topical solutions or baths or by drinking H2-enriched water. This latter method is the easiest and least costly method of administration. There are no safety issues with hydrogen;it has been used for years in gas mixtures for deep diving and in numerous clinical trials without adverse events, and there are no warnings in the literature of its toxicity or long-term exposure effects. Molecular hydrogen has proven useful and convenient as a novel antioxidant and modifier of gene expression in many conditions where oxidative stress and changes in gene expression result in cellular damage.

Family Environment Factors to Impact on the Effect of the Smoking Prevention Educational Program for Elementary and Junior High School Students

Smoking is a major health problem in many countries. It has been reported on the effects of education on youth with a reduced smoking rate and developed awareness of avoiding smoking verified as a result of educational intervention. The aim of this study was to verify the relationship between sex, school age, and family smoking and the effectiveness of smoking prevention education program (SPEP) as factors that impact the effectiveness of SPEP in elementary school and junior high school students. The participants in this survey were 6676 students, who attended elementary and junior high schools in Tokushima Prefecture between 2011 and 2015, and attended the SPEP. As factors that influence the effectiveness of the SPEP, we examined school types, sex, smokers in the family. Participants were asked the following questions before and after the SPEP to measure awareness of and attitudes toward smoking: “intention not to smoke cigarettes as adults”, “intention to refuse cigarettes when offered”, “attitude of staying away from smokers”, and “desire that their family will not smoke”. The number of survey collected was 6676, with effective responses from 5974 (90%). Among the 5974, there were 2963 (50%) males and 3011 (50%) females, 5106 elementary school students (86%), and 868 junior high school students (15%). In the case of smoker mother, it was difficult to improve these children’s “intention not to smoke as adults”, “intention to refuse cigarettes when offered”, and smoker father, it was difficult to improve these children’s “attitude of staying away from smokers”, and “desire that their family will not smoke”. Especially, in the case of smoker parents, it was particularly difficult for the SPEP to be effective in improving awareness of and attitudes toward smoking among elementary and junior high school students.

Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?

BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.

Pathological and physiological functional cross-talks ofα-synuclein and tau in the central nervous system

α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons,respectively.Previous works have revealed that intracellular deposition ofα-synuclein and/or tau causes many neurodegenerative disorders,including Alzheimer’s disease and Parkinson’s disease.Despite intense investigation,the normal physiological functions and roles ofα-synuclein and tau are still unclear,owing to the fact that mice with knockout of either of these proteins do not present apparent phenotypes.Interestingly,the co-occurrence ofα-synuclein and tau aggregates was found in post-mortem brains with synucleinopathies and tauopathies,some of which share similarities in clinical manifestations.Furthermore,the direct interaction ofα-synuclein with tau is considered to promote the fibrillization of each of the proteins in vitro and in vivo.On the other hand,our recent findings have revealed thatα-synuclein and tau are cooperatively involved in brain development in a stage-dependent manner.These findings indicate strong cross-talk between the two proteins in physiology and pathology.In this review,we provide a summary of the recent findings on the functional roles ofα-synuclein and tau in the physiological conditions and pathogenesis of neurodegenerative diseases.A deep understanding of the interplay betweenα-synuclein and tau in physiological and pathological conditions might provide novel targets for clinical diagnosis and therapeutic strategies to treat neurodegenerative diseases.

Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis

BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical issues.METHODS We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center.All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled.Patients were followed up until August 2020.The primary outcome was the clinical response rate at week 8.Secondary outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week 48.RESULTS The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,respectively.The overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after re-increase.All 6 patients with herpes zoster(HZ)developed the infection after achieving remission by TOF.CONCLUSION TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-αagents.Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF.Special attention is needed for tapering and HZ.

Intranasal administration of stem cell-derived exosomes for central nervous system diseases

Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.

Rebuilding insight into the pathophysiology of Alzheimer’s disease through new blood-brain barrier models

The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous system.Blood-brain barrier breakdown is a common pathology in various neurological diseases,such as Alzheimer’s disease,stroke,multiple sclerosis,and Parkinson’s disease.Traditionally,it has been considered a consequence of neuroinflammation or neurodegeneration,but recent advanced imaging techniques and detailed studies in animal models show that blood-brain barrier breakdown occurs early in the disease process and may precede neuronal loss.Thus,the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective therapeutics.To elucidate the molecular mechanism underlying blood-brain barrier breakdown and translate them into therapeutic strategies for neurological diseases,there is a growing demand for experimental models of human origin that allow for functional assessments.Recently,several human induced pluripotent stem cell-derived blood-brain barrier models have been established and various in vitro blood-brain barrier models using microdevices have been proposed.Especially in the Alzheimer’s disease field,the human evidence for blood-brain barrier dysfunction has been demonstrated and human induced pluripotent stem cell-derived blood-brain barrier models have suggested the putative molecular mechanisms of pathological blood-brain barrier.In this review,we summarize recent evidence of blood-brain barrier dysfunction in Alzheimer’s disease from pathological analyses,imaging studies,animal models,and stem cell sources.Additionally,we discuss the potential future directions for blood-brain barrier research.

Paradigm shift in cancer treatment: Cancer treatment as a metabolic disease-fusion of Eastern and Western medicine

Current standard therapies for cancer,including surgery,anti-cancer drugs,and radiotherapy,are thought to contribute to the improvement in the survival rates of cancer patients.However,such standard therapies have 3 major problems:in advanced cancers,it is unlikely that standard cancer treatments will cure the disease;adverse side effects that accompany standard cancer treatments put many patients in distress;and a large amount of medical expenditure is required for new and expensive anti-cancer drugs.These problems may be viewed as a result of establishing treatments without any consideration regarding the root cause of the cancer.Otto Warburg suggested that particular changes in the energy metabolism of cells,which are associated with a shortage of oxygen,are the root cause of cancer.Cancer cells have unique metabolic characteristics,and thus we believe that it is important to treat cancer as a metabolic disease.More specifically,not only is it important to suppress cancer cell metabolism,but it is also important to improve the chronic inflammation that is associated with the development and progression of cancer,and to support the functions of immune cells.This type of view of cancer treatment coincides with the principles of Chinese medicine,which has a history of 4000 years,such as 'fuzheng quxie' and 'zhibing qiuben',which can assist in the establishment of cancer treatments for patients.In this article,we discuss cancer treatments from the view of cancer as a metabolic disease and their association with Chinese medicine,and introduce some clinical cases along with a review of the literature.

Improvement of decocting method for Kampo medicines using a microwave oven to extend its applications in clinical practice

Decoction of Kampo medicines plays an important role in clinical practice, especially in individualized treatment, while the inconvenience and a long time requirement of the decocting process are impediments to its widespread use in Japan. In this study, we improved the decocting method by using a microwave oven such as those found in most kitchens. To validate the feasibility and safety of this new method, we decocted kakkonto, which is the most widely used formula in clinical treatment in Japan, and keishikabushito, which contains toxic components using a microwave oven. Regarding the contents of 8 characteristic components in the kakkonto decoction and the contents of 6 toxic components in the keishikabushito decoction as indices, and with the extraction and detoxification effects equal to those of the conventional decocting method as targets, we optimized the decocting conditions with Response Surface Methods. With this new method, it took 35 min to obtain almost the same extraction effect for kakkonto as with the conventional decocting method, which takes 40 min;meanwhile, it took only 45 min to detoxify keishikabushito, which takes 60 min using the conventional decocting method. Decocting Kampo medicines with a microwave oven is feasible and as safe as the conventional decocting method. It is a convenient, safe, time-saving method, and may be applied widely in clinical practice. This innovation should allow more patients to benefit from decoction and the individualized treatment it offers.

Schizophrenia knowledge and attitudes toward help-seeking among Japanese fathers and mothers of high school students

The prodromal symptoms of schizophrenia are nonspecific and include social withdrawal, sleeplessness, decreased desire, and loss of concentration. Schizophrenia outcomes might be improved if greater therapeutic effort was focused on people with prodromal symptoms. To hasten help-seeking for schizophrenia, we developed a schizophrenia education program for families of patients. Help-seeking and schizophrenia attitudes and knowledge were analyzed among Japanese parents (666 fathers and 613 mothers) of high school students by using the Social Distance Scale-Japanese version, the Link Devaluation-Discrimination Measure and our own questions on help-seeking and schizophrenia knowledge. Statistical analysis included cross-tabulation, the χ2 test, and multiple regression analysis. Most (97.5%) fathers were aged 40 - 59 years;most (78.3%) mothers were aged 40 - 49 years. There was a significant difference between fathers and mothers in basic knowledge of schizophrenia (P < 0.001);however, fathers and mothers did not significantly differ in their attitudes toward schizophrenia (P > 0.05). When asked what treatment they would seek for a child with sleeplessness or social withdrawal, fathers and mothers significantly differed in seeking help medical care at a department of psychosomatic medicine (P < 0.05) and in seeking help from the nurse at their child’s school (P < 0.001). Fathers and mothers also differed in relation to the decision not to seek help (P < 0.001). Multiple regression analysis revealed that basic knowledge significantly differed between fathers and mothers (P = 0.001). In an analysis of parental response to a child with sleepiness and social withdrawal, multiple regression analysis revealed that fathers and mothers significantly differed in the likelihood of seeking help at a department of psychosomatic medicine and from a school nurse and in the likelihood of not seeking help (P < 0.05, P = 0.001 and P = 0.001, respectively). In conclusion, help-seeking behavior differed between Japanese fathers and mothers. These findings should assist in developing schizophrenia education programs that aim to hasten intervention.

Variations in the mental health and sense of coherence (SOC) of new graduate nurses and the effects of SOC on variations in mental health

The current research conducted a longitudinal study of new graduate nurses at 3 times-prior to their employment as nurses and 3 months and 1 year afterward. This study yielded 3 findings. 1) The mental health of new graduate nurses significantly worsens 3 months after employment as a nurse and mental health 1 year after employment as a nurse was significantly worse than that before employment. 2) A sense of coherence (SOC) is the ability to cope with stressors, and the 3 components of SOC decreased significantly in the year after employment as a nurse. 3) The mental health of new graduate nurses was significantly affected by a low SOC and by previous diminishing of SOC. Findings suggested the importance of support to sustain and improve the mental health of new graduate nurses and the importance of approaches in the workplace to encourage the development of SOC.

A clue to potential therapeutic targets: application of integrative medicine and bioinformatics

More and more evidence show that the targets of traditional Chinese medicine are a resource pool that contributes to the modern medicine. A key aspect of medicine research is to address the issue how to look for a clue of potential therapeutic molecular targets by interdisciplinary approaches. With the development of high throughput technology, a considerable amount of data has been emerging. The application of these big data is not so efficient as the generation of them. This paper attempts to show that interdisciplinary analysis contributes to the discovery of targets at the initial stage of drug research, indicating that it is necessary to explore the drug research and development with interdisciplinary approaches between integrative medicine and bioinformatics.