著者

Jianjun Gao Shasha Hu

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

BioScience Trends (ISSN:18817815)

巻号頁・発行日

vol.14, no.2, pp.156-158, 2020-04-30 (Released:2020-05-21)

参考文献数

17

被引用文献数

15 38

---

Drugs that are specifically efficacious against SARS-CoV-2 have yet to be established. Chloroquine and hydroxychloroquine have garnered considerable attention for their potential to treat coronavirus disease 2019 (COVID-19). Increasing evidence obtained from completed clinical studies indicates the prospects for chloroquine/hydroxychloroquine to treat COVID-19. More randomized control clinical studies are warranted to determine the feasibility of these two drugs in treating COVID-19.

著者

Zhenwei Wang Xiaorong Chen Yunfei Lu Feifei Chen Wei Zhang

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

BioScience Trends (ISSN:18817815)

巻号頁・発行日

vol.14, no.1, pp.64-68, 2020-02-29 (Released:2020-03-16)

参考文献数

11

被引用文献数

179 368

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Pneumonia associated with the 2019 novel coronavirus (2019-nCoV) is continuously and rapidly circulating at present. No effective antiviral treatment has been verified thus far. We report here the clinical characteristics and therapeutic procedure for four patients with mild or severe 2019-nCoV pneumonia admitted to Shanghai Public Health Clinical Center. All the patients were given antiviral treatment including lopinavir/ritonavir (Kaletra®), arbidol, and Shufeng Jiedu Capsule (SFJDC, a traditional Chinese medicine) and other necessary support care. After treatment, three patients gained significant improvement in pneumonia associated symptoms, two of whom were confirmed 2019-nCoV negative and discharged, and one of whom was virus negative at the first test. The remaining patient with severe pneumonia had shown signs of improvement by the cutoff date for data collection. Results obtained in the current study may provide clues for treatment of 2019-nCoV pneumonia. The efficacy of antiviral treatment including lopinavir/ritonavir, arbidol, and SFJDC warrants further verification in future study.

著者

Jufeng Xia Shuichi Minamino Kazuma Kuwabara

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

BioScience Trends (ISSN:18817815)

巻号頁・発行日

pp.2020.03308, (Released:2020-09-06)

参考文献数

59

被引用文献数

24

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Since the approval in 2017 and the amazing achievement of Kymriah and Yescarta, the number of basic researchers and clinical trials investigating the safety and efficacy of chimeric antigen receptor-expressing T cells (CAR-T cells) has been relentlessly increasing. Up to now, more than 200 clinical trials are listed on clinical trial database of NIH and the basic research is countless. However, the production of allogeneic CAR-T cells products is still expensive and has toxicity. Thus, more effort is needed to develop reliable off-the-shelf cellular therapeutic methods with safety and efficiency for the treatment of patients with cancer. As a kind of innate effector lymphocyte with potent antitumor activity, natural killer cells (NK cells) have attracted much attention. Until now, basic and clinical research has shown that chimeric antigen receptor-expressing NK cell (CAR-NK) therapy may play a significant anti-tumor role and its safety is higher than CAR-T cell therapy. In this review, we discuss advantages and shortages of employing CAR-NK cells as a novel cellular therapy against cancer.

著者

Sho Nishiguchi Nagisa Sugaya Kentaro Sakamaki Shunsaku Mizushima

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

BioScience Trends (ISSN:18817815)

巻号頁・発行日

vol.11, no.1, pp.54-61, 2017-02-28 (Released:2017-03-22)

参考文献数

39

被引用文献数

2 11

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The end-of-life (EOL) care bonus introduced by the Japanese government works as a financial incentive and framework of quality preservation, including advance care planning, for EOL care among nursing home residents. This study aims to clarify the effects of the EOL care bonus in promoting EOL care in nursing homes. A longitudinal observational study using a questionnaire was conducted. We invited 378 nursing homes in Kanagawa prefecture in Japan, a region with a rapidly aging population, to participate in the study. The outcome was the number of residents dying in nursing homes from 2004 to 2014. In a linear mixed model, fixed-effect factors included year established, unit care, regional elderly population rate and hospital beds, adjacent affiliated hospital, full-time physician on site, physician's support during off-time, basic EOL care policy, usage of the EOL care bonus, EOL care conference, and staff experience of EOL care. A total of 237 nursing home facilities responded (62.7%). The linear mixed model showed that the availability of the EOL care bonus (coefficient 3.1, 95 % CI 0.67-5.51, p = 0.012) and years of usage of the EOL care bonus (p < 0.001) were significantly associated with increased numbers of residents dying in nursing homes. Our analysis revealed that the EOL care bonus has the potential to increase the number of residents receiving EOL care in nursing homes over several years. EOL care conferences, physician support for emergency care during off-time, and the presence of an adjacent affiliated hospital may also increase the number of residents receiving EOL care in nursing homes. These results suggest that a government financial incentive may contribute to effective EOL care among nursing home residents in other developed countries with rapidly aging populations.

著者

Genya Kobayashi Shonosuke Sugasawa Hiromasa Tamae Takayuki Ozu

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

BioScience Trends (ISSN:18817815)

巻号頁・発行日

pp.2020.03133, (Released:2020-05-28)

参考文献数

15

被引用文献数

30

---

Japan has observed a surge in the number of confirmed cases of the coronavirus disease (COVID-19) that has caused a serious impact on the society especially after the declaration of the state of emergency on April 7, 2020. This study analyzes the real time data from March 1 to April 22, 2020 by adopting a sophisticated statistical modeling based on the state space model combined with the well-known susceptible-infected-recovered (SIR) model. The model estimation and forecasting are conducted using the Bayesian methodology. The present study provides the parameter estimates of the unknown parameters that critically determine the epidemic process derived from the SIR model and prediction of the future transition of the infectious proportion including the size and timing of the epidemic peak with the prediction intervals that naturally accounts for the uncertainty. Even though the epidemic appears to be settling down during this intervention period, the prediction results under various scenarios using the data up to May 18 reveal that the temporary reduction in the infection rate would still result in a delayed the epidemic peak unless the long-term reproduction number is controlled.

著者

Talakola Naveen Ashutosh Biswas Naveet Wig Manish Soneja Pankaj Jorwal Chitikela Sindhura Durga Paras Singla Charusmita Chaudhary Upendra Baitha

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.13, no.1, pp.59-61, 2019-02-28 (Released:2019-03-16)

参考文献数

7

被引用文献数

1

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Familial hypercholesterolemia (FH) is a form of primary hyperlipoproteinemia characterized by the presence of high concentrations of serum low density lipoprotein (LDL) cholesterol, increased tendency to form xanthomas and early onset of coronary artery disease. This disease is an autosomal dominant disorder caused by defects in the gene that encode for the LDL receptor. Homozygous familial hypercholesterolemia is a rare occurrence and here we report a case of an 18-year-old girl with familial hypercholesterolemia treated with anti-lipidemic drugs and controlled only with LDL apheresis. The patient expired after 3 months highlighting the difficulties in management due to economic constraints in a resource limited setting in spite of availability of effective therapy.

著者

Fabian Grass Matthieu Cachemaille David Martin Nicolas Fournier Dieter Hahnloser Catherine Blanc Nicolas Demartines Martin Hübner

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

BioScience Trends (ISSN:18817815)

巻号頁・発行日

vol.12, no.1, pp.47-53, 2018-02-28 (Released:2018-03-18)

参考文献数

37

被引用文献数

12

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The purpose of this prospective cohort study was to compare multimodal pain management and pain perception after open vs. laparoscopic colorectal surgery within enhanced recovery care. Pain scores at rest and at mobilization were prospectively assessed in consecutive patients using Visual Analog Scales (VAS 0-10) and consumption of different analgesics was recorded daily until 96 hours postoperatively. Uni- and multivariate risk factors for pain peaks (≥ 4/10) were identified by logistic regression and compared between two propensity score matched groups (open vs. laparoscopic). 156 open and 176 laparoscopic procedures were included. Mean VAS scores were consistently < 3 until 96 hours at rest and at mobilization. Patients operated by laparoscopy experienced more pain peaks (≥ 4) within 24 hours (p < 0.05), while patients operated by open approach experienced more pain peaks (≥ 4) during mobilization at 72 hours (p < 0.05). Independent risk factors for insufficient pain control (≥ 4) within 24 hours from surgery were duration of the procedure (OR 3.37, 95%CI 2.03-5.59), emergency surgery (OR 3.01, 95%CI 1.72-5.31), wound infiltration (OR 3.23, 95%CI 0.97-10.70), age < 70 years (OR 2.03, 95% CI 1.18-3.48) and ASA I-II score (OR 2.06, 95% CI 1.19-3.56). The perioperative adding of lidocaine ± ketamine to opioids did not improve postoperative pain perception nor decrease morphine equivalents. In conclusion, overall pain scores were low after colorectal surgery. However, pain peaks remained a concern early after minimally invasive surgery and after epidural removal for open surgery. Multimodal strategies were not superior to opioids alone.

著者

Ya-Nan Ma Xuemei Jiang Wei Tang Peipei Song

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

BioScience Trends (ISSN:18817815)

巻号頁・発行日

vol.17, no.5, pp.335-355, 2023-10-31 (Released:2023-11-18)

参考文献数

165

被引用文献数

3

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Studies have found that intermittent fasting (IF) can prevent diabetes, cancer, heart disease, and neuropathy, while in humans it has helped to alleviate metabolic syndrome, asthma, rheumatoid arthritis, Alzheimer's disease, and many other disorders. IF involves a series of coordinated metabolic and hormonal changes to maintain the organism's metabolic balance and cellular homeostasis. More importantly, IF can activate hepatic autophagy, which is important for maintaining cellular homeostasis and energy balance, quality control, cell and tissue remodeling, and defense against extracellular damage and pathogens. IF affects hepatic autophagy through multiple interacting pathways and molecular mechanisms, including adenosine monophosphate (AMP)-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), silent mating-type information regulatory 2 homolog-1 (SIRT1), peroxisomal proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR), as well as signaling pathways and molecular mechanisms such as glucagon and fibroblast growth factor 21 (FGF21). These pathways can stimulate the pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), play a cytoprotective role, downregulate the expression of aging-related molecules, and prevent the development of steatosis-associated liver tumors. By influencing the metabolism of energy and oxygen radicals as well as cellular stress response systems, IF protects hepatocytes from genetic and environmental factors. By activating hepatic autophagy, IF has a potential role in treating a variety of liver diseases, including non-alcoholic fatty liver disease, drug-induced liver injury, viral hepatitis, hepatic fibrosis, and hepatocellular carcinoma. A better understanding of the effects of IF on liver autophagy may lead to new approaches for the prevention and treatment of liver disease.

著者

Mohamad Moussa Athanasios G. Papatsoris Mohamad Abou Chakra Youssef Fares Baraa Dabboucy Athanasios Dellis

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.10, no.1, pp.1-10, 2021-02-28 (Released:2021-03-04)

参考文献数

95

被引用文献数

2 6

---

Spina bifida (SB) is a neurogenetic disorder with a complex etiology that involves genetic and environmental factors. SB can occur in two major forms of open SB or SB aperta and closed SB or SB occulta. Myelomeningocele (MMC), the most common neural tube defects (NTDs), occurs in approximately 1 in 1,000 births. Considering non-genetic factors, diminished folate status is the best-known factor influencing NTD risk. The methylenetetrahydrofolate reductase (MTHFR) gene has been implicated as a risk factor for NTDs. The primary disorder in the pathogenesis of MMC is failed neural tube closure in the embryonic spinal region. The clinical manifestation of SB depends on clinical type and severity. SB can be detected in the second trimester using ultrasound which will reveal specific cranial signs. The management of MMC traditionally involves surgery within 48 h of birth. Prenatal repair of MMC is recommended for fetuses who meet maternal and fetal Management of Myelomeningocele Study (MOMS) specified criteria. Urological manifestations of SB include urinary incontinence, urolithiasis, sexual dysfunction, renal dysfunction, and urinary tract infection. Renal failure is among the most severe complications of SB. The most important role of the urologist is the management of neurogenic bladder. Medical management with clean intermittent catheterization and anticholinergic treatment is generally considered the gold standard of therapy. However, when this therapy fails surgical reconstruction become the only remaining option. This review will summarize the pathogenesis, risk factors, genetic contribution, diagnostic test, and management of SB. Lastly, the urologic outcomes and therapies are reviewed.

著者

Binh Cao Quan Nguyen Kazuki Yoshimura Shigenori Kumazawa Shinkichi Tawata Hiroshi Maruta

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.11, no.2, pp.110-114, 2017-04-30 (Released:2017-05-30)

参考文献数

13

被引用文献数

36 43

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A sulfated saponin called "Frondoside A" (FRA) from sea cucumber and ingredients from Okinawa propolis (OP) have been previously shown to suppress the PAK1-dependent growth of A549 lung cancer as well as pancreatic cancer cells. However, the precise molecular mechanism underlying their anti-cancer action still remains to be clarified. In this study, for the first time, we found that both FRA and OP directly inhibit PAK1 in vitro in a selective manner (far more effectively than two other oncogenic kinases, LIMK and AKT). Furthermore, at least two major anti-cancer ingredients of OP, nymphaeols A and C, also directly inhibit PAK1 in vitro in a selective manner. To the best of our knowledge, FRA is the first marine compound that selectively inhibits PAK1. Likewise, these nymphaeols are the first propolis ingredients that selectively inhibit PAK1.

著者

Alexandre Fabre Julien Mancini

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

pp.2022.01063, (Released:2022-07-22)

参考文献数

14

---

LUCA, the last universal common ancestor, is the hypothetical most recent common ancestor of the three domains of life which share the universal genes (UG). It seems interesting to evaluate whether the UG phylogeny has had an impact on current Human gene constraints. A list of human homologs of UG was retrieved from the eggNOG database. We analyzed this LUCA gene (LG) group, and a random sample of 500 genes from the gnomAD database (RG group). Gene constraint metrics were retrieved from gnomAD and associations with Mendelian diseases and modes of inheritance were retrieved from OMIM. The LG group consisted of 277 genes and the RG group, 492 (8 genes were in LG group). 38.6% of the genes in the LG group and 25.2% of the genes in the RG group were associated with a Mendelian disease (p < 0.0001). The mode of inheritance was more often autosomal recessive (69.0 vs. 50.5%), and less often autosomal dominant (19.0 vs. 31.3%), or mixed (6.0 vs. 12.1%) for those associated with the LG group (p = 0.048). The LG group was significantly more constrained for missense variants (MOEUF, 0.919 vs. 0.997, p < 0.0001) and was borderline significantly more constrained for loss-of-function variants (LOEUF, 0.872 vs. 0.947, p = 0.051). These results suggest that the UG in humans differs from the rest of the genome in terms of constraints and associated Mendelian diseases. It suggests that phylogenic data can explain some of the characteristics of human genes and could help in interpreting variants.

著者

Jing Cao Yirong Shi Min Wen Yuanyuan Peng Qiqi Miao Xiaoning Liu Mingbin Zheng Tetsuya Asakawa Hongzhou Lu

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

BioScience Trends (ISSN:18817815)

巻号頁・発行日

pp.2022.01495, (Released:2022-12-09)

参考文献数

20

被引用文献数

4

---

Chlorine dioxide (ClO2) is a high-level disinfectant that is safe and widely used for sterilization. Due to the limitations on preparing a stable solution, direct use of ClO2 in the human body is limited. Nasal irrigation is an alternative therapy used to treat respiratory infectious diseases. This study briefly summarizes the available evidence regarding the safety/efficacy of directly using ClO2 on the human body as well as the approach of nasal irrigation to treat COVID-19. Based on the available information, as well as a preliminary experiment that comprehensively evaluated the efficacy and safety of ClO2, 25-50 ppm was deemed to be an appropriate concentration of ClO2 for nasal irrigation to treat COVID-19. This finding requires further verification. Nasal irrigation with ClO2 can be considered as a potential alternative therapy to treat respiratory infectious diseases, and COVID-19 in particular.

著者

Yanqin Lu Qingxia Gao Xiuzhi Ren Junfeng Li Dan Yang Zijian Zhang Jinxiang Han

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.11, no.3, pp.96-104, 2022-08-31 (Released:2022-09-17)

参考文献数

53

被引用文献数

6

---

The current study updated data on the incidence and prevalence of 121 rare diseases listed in China's First List of Rare Diseases to provide rationales and references for the development and promotion of rare-disease-related policies. The National Health Commission of the People's Republic of China issued the Rare Disease Diagnosis and Treatment Guide (2019) (denoted here as China's Rare Disease Diagnosis and Treatment Guide). Then 121 diseases were registered with the national rare disease diagnosis and treatment network. The incidence/prevalence of 121 rare diseases varied from country to country. Data are available for a total of 76 rare diseases (76 of 121 rare diseases, 62.81%) in China, including data on the incidence of 23 rare diseases (19.01%) and data on the prevalence of 66 (54.55%). There are data on the incidence/prevalence of 112 rare diseases (112 of 121 rare diseases, 92.56%) at the global level, including data on the incidence of 86 rare diseases (71.07%) and data on the prevalence of 91 (75.21%). On average, the incidence of progressive muscular dystrophies, hyperphenylalaninemia, citrullinemia, and methylmalonic acidemia is over 1/10,000 in China. The prevalence of coronary artery ectasia, congenital scoliosis, retinitis pigmentosa, severe congenital neutropenia, congenital hyperinsulinemic hypoglycemia, and osteogenesis imperfecta is over 1/10,000 in China. All of these figures are beyond the cut-off of 1/10,000 according to the 2021 definition of rare diseases in China. As registration and investigation of rare diseases continues, the spectrum of rare diseases in some provinces is expanding. Diseases such as idiopathic pulmonary arterial hypertension, hepatolenticular degeneration, hemophilia, amyotrophic lateral sclerosis, idiopathic pulmonary fibrosis, and multiple sclerosis are relatively prevalent in some regions and cities of China. Registration efforts promote the correction of incidence/prevalence data, development of orphan drugs, coverage by medical insurance, and development of clinical and diagnostic pathways.

著者

Atsushi Miyashita Kazuhisa Sekimizu Chikara Kaito

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

pp.2022.01058, (Released:2022-09-06)

参考文献数

25

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Male crickets emit acoustic signals (i.e., songs) by chirping using their forewings. Although the mechanisms and adaptive functions of these songs are well studied, knowledge about how songs develop within a generation is relatively scarce. Our previous work demonstrated a stable peak frequency at 5.7 kHz in the calling songs recorded from mature adult male crickets (Gryllus bimaculatus). In the present study, we monitored changes in the frequency component over time from the sexual maturity stage (early adult stage). We recorded 300 calling songs from a pool of 122 adults. The peak frequency distribution was lower and unstable (i.e., greater coefficient of variance) in the early adult stage. The mean peak frequency was 4.9 kHz on day 3, but gradually converged to 5.8 kHz over the 2-week adult stage. Immature adult males (emitting immature songs) produced an appropriately tuned song with a peak frequency of 5.8 kHz in an environment of 80% helium and 20% oxygen. These results suggest that the frequency component of the calling song is acquired during the early to mid-adult stage, and may be related to sexual maturation in males. Findings from the helium substitution experiment revealed that physical resistance from surrounding gas molecules negatively affect the stability of male singing, and that muscle development and forewing hardening may contribute to the maturation of singing, suggesting that females may adaptively select sexually mature males based on song traits.

著者

Wei Qin Yirong Shi Weimei Chen Xiaokang Jia Tetsuya Asakawa

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

BioScience Trends (ISSN:18817815)

巻号頁・発行日

pp.2022.01352, (Released:2022-08-24)

参考文献数

56

被引用文献数

6

---

By far, no revolutionary breakthrough in the treatment of Parkinson's disease (PD) was found. It is indeed a knotty problem to select a satisfactory strategy for treating some patients with advanced stage PD. Development of novel therapeutic targets against PD has been an urgent task faced by global PD researchers. Targets in the tryptophan–kynurenine pathway (KP) were then considered. Metabolites in the KP are liposoluble. Some neurotoxic metabolites, including 3-hydroxykynurenine and its downstream 3-hydroxyanthranilic acid and quinolinic acid, are mainly produced peripherally. They can easily cross the blood–brain barrier (BBB) and exert their neurotoxic effects in the central neuron system (CNS), which is considered as a potential pathophysiological mechanism of neurodegenerative diseases. Hence, agents against the targets in the KP have two characteristics: (1) being independent from the dopaminergic system and (2) being seldom affected by the BBB. Inspiringly, one agent, namely, the inhibitor of indoleamine 2,3-dioxygenase 1, has been currently reported to present satisfactory efficacy comparable to levodopa, implying that the KP might be a potential novel target for PD. This review collected and summarized the updated information regarding the association of the KP with PD, which is helpful for understanding the clinical value of the KP in the PD scenario.

著者

Katherine M. Morgan Shabbar Danish Zhenggang Xiong

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Intractable & Rare Diseases Research (ISSN:21863644)

巻号頁・発行日

vol.11, no.1, pp.43-45, 2022-02-28 (Released:2022-03-08)

参考文献数

10

被引用文献数

2

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Molecular alterations found in gliomas are now considered entity-defining features. The World Health Organization (WHO) classification system currently classifies the vast majority of gliomas utilizing an integrated genotype-phenotype approach. We present a case of diffuse astrocytoma with a mosaic isocitrate dehydrogenase (IDH)1-R132H-mutant immunophenotype and low subclonal allele frequency. A 35-year-old patient with a history of IDH1-R132H mutated diffuse astrocytoma in 20014 presented to the hospital again in 2019. MRI examination showed a non-enhancing abnormal signal in the periphery of her previous surgical cavity. Histopathological examination revealed that the tumor was hypercellular and without high grade histopathological features. The neoplastic cells were immunohistologically positive for GFAP, Olig2, and ATRX. However, only some scattered tumor cells were positive for IDH1-R132H. Cytogenetic studies revealed a lack of chromosomal 1p/19q co-deletion. Further next-generation sequencing (NGS) demonstrated a low-level IDH1-R132H mutation and allele frequency. Based on these findings, the diagnosis of diffuse astrocytoma with mosaic IDH1-R132H-mutant immunophenotype and low subclonal allele frequency (WHO grade II) was generated. This case indicates that gliomas may have heterogeneous molecular profile and the intra-tumoral molecular heterogeneity highlights the need to further characterize the molecular profile for glioma classification and clinical management.

著者

Kenichiro Sato Yoshiki Niimi Tatsuo Mano Atsushi Iwata Takeshi Iwatsubo

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

BioScience Trends (ISSN:18817815)

巻号頁・発行日

pp.2022.01115, (Released:2022-04-20)

参考文献数

18

被引用文献数

1

---

Whether there are differences in the time to onset of drug-induced parkinsonism (DIP) depending on the type of drugs causing DIP remains uncertain, so that question was investigated here using a large real-world database. Fourteen DIP-related drug categories were defined to perform a disproportionality analysis using a large Japanese pharmacovigilance database containing more than 600,000 self-reported adverse events (AEs) recorded between April 2004 and September 2021 to identify AEs indicating "parkinsonism" in association with the defined drug categories. The time from drug administration to the onset of DIP was comparatively analyzed. Results indicated that the median time to onset was shorter than 1 month in more than half of the cases of DIP; it was shortest with peripheral dopamine antagonists (median: 0.1 weeks), followed by benzodiazepine (median: 0.5 weeks), butyrophenone (median: 0.7 weeks), novel antidepressants (median: 2.5 weeks), atypical antipsychotics (median: 3.3 weeks), other antidepressants (e.g., lithium, median: 3.7 weeks), and benzamide (median: 4.5 weeks). In contrast, anti-dementia drugs, tricyclic antidepressants, and antiepileptic drugs resulted in a relatively longer time to onset (median: 9.9, 17.2, and 28.4 weeks, respectively). In addition, a maximum delay of even longer than 2 years was reported for benzamide (846 weeks), anti-Parkinsonism drugs (382 weeks), phenothiazine (232 weeks), atypical antipsychotics (167 weeks), anti-dementia drugs (161 weeks), and benzodiazepines (120 weeks). The current results suggested that the characteristics of the time to onset of DIP may substantially differ depending on the type of drug causing that DIP. This finding may help when diagnosing patients with parkinsonism.

著者

Jianjun Gao Fusheng Sun

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.15, no.6, pp.281-288, 2021-12-31 (Released:2022-01-15)

参考文献数

76

被引用文献数

6

---

Coronavirus disease 2019 (COVID-19) has had a significant impact on human health and economic development over the past two years. Therapeutics in combination with vaccines are critical measures to fight the pandemic. The three areas of drug development are blocking the entry of SARS-CoV-2 into cells, suppressing viral replication inside cells, and regulating the immune system, and important advances have recently been made in those areas. Increasing numbers of neutralizing antibodies and small molecules that show promise have been fully approved or authorized for emergency use, resulting in decreased mortality of patients with COVID-19. The use of therapeutics will have a great impact on formulating and revising public policies to control the pandemic. The pace of lifting of restrictions and economic recovery worldwide will also accelerate in the future. Here, the drugs or agents that have attracted considerable attention and that have led to remarkable progress in the fight against COVID-19 are reviewed

著者

Surachai Ngamratanapaiboon Pracha Yambangyang

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

vol.15, no.6, pp.317-324, 2021-12-31 (Released:2022-01-15)

参考文献数

30

被引用文献数

3

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Most studies of antipsychotic-therapies have highlighted the discrepancy between plasma and brain pharmacokinetics of antipsychotics, but how the drug changes through the blood brain barrier (BBB) has not been investigated. Cell-based metabolomics using liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis were applied for screening of antipsychotic metabolites in the BBB. We applied this approach to analyze the antipsychotic biotransformation in brain microvascular endothelia cells (BMVECs), the main component of the BBB. From this study, five, four, three, and one metabolite of chlorpromazine, clozapine, haloperidol and risperidone, respectively, were locally metabolized on the BMVECs. These results confirm that there is a drug biotransformation process within the BBB and show that drug metabolite screening employed cell-based metabolomics using LC-MS, combined with multivariate analysis in the study of BMVECs exposed to antipsychotics can provide a way to screen drug metabolites in the BBB.

著者

Itsuro Kazama

出版者

International Research and Cooperation Association for Bio & Socio-Sciences Advancement

雑誌

Drug Discoveries & Therapeutics (ISSN:18817831)

巻号頁・発行日

pp.2020.03046, (Released:2020-06-25)

参考文献数

18

被引用文献数

3 17

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In the midst of a pandemic, finding effective treatments for coronavirus disease 2019 (COVID-19) is the urgent issue. In "chronic inflammatory diseases", the overexpression of delayed rectifier K+-channels (Kv1.3) in leukocytes is responsible for the overactivation of cellular immunity and the subsequent cytokine storm. In our previous basic studies, drugs including chloroquine and azithromycin strongly suppressed the channel activity and pro-inflammatory cytokine production from lymphocytes. These findings suggest a novel pharmacological mechanism by which chloroquine, with or without azithromycin, is effective for severe cases of COVID-19, in which the overactivation of cellular immunity and the subsequent cytokine storm are responsible for the pathogenesis.