Computer Science Technology in Natural Products Research: A Review of Its Applications and Implications.

Computational approaches to drug development are rapidly growing in popularity and have been used to produce significant results. Recent developments in information science have expanded databases and chemical informatics knowledge relating to natural products. Natural products have long been well-studied, and a large number of unique structures and remarkable active substances have been reported. Analyzing accumulated natural product knowledge using emerging computational science techniques is expected to yield more new discoveries. In this article, we discuss the current state of natural product research using machine learning. The basic concepts and frameworks of machine learning are summarized. Natural product research that utilizes machine learning is described in terms of the exploration of active compounds, automatic compound design, and application to spectral data. In addition, efforts to develop drugs for intractable diseases will be addressed. Lastly, we discuss key considerations for applying machine learning in this field. This paper aims to promote progress in natural product research by presenting the current state of computational science and chemoinformatics approaches in terms of its applications, strengths, limitations, and implications for the field.

Quantitative Assessment of Intervertebral Disc Composition by MRI: Sensitivity to Diurnal Variation.

Whether diurnal variation exists in quantitative MRI indices such as the T1rho relaxation time (T1ρ) of the intervertebral disc (IVD) is yet to be explored. This prospective study aimed to evaluate the diurnal variation in T1ρ, apparent diffusion coefficient (ADC), and electrical conductivity (σ) of lumbar IVD and its relationship with other MRI or clinical indices. Lumbar spine MRI, including T1ρ imaging, diffusion-weighted imaging (DWI), and electric properties tomography (EPT), was conducted on 17 sedentary workers twice (morning and evening) on the same day. The T1ρ, ADC, and σ of IVD were compared between the time points. Their diurnal variation, if any, was tested for correlation with age, body mass index (BMI), IVD level, Pfirrmann grade, scan interval, and diurnal variation in IVD height index. The results showed a significant decrease in T1ρ and ADC and a significant increase in the σ of IVD in the evening. T1ρ variation had a weak correlation with age and scan interval, and ADC variation with scan interval. Diurnal variation exists for the T1ρ, ADC, and σ of lumbar IVD, which should be accounted for in image interpretation. This variation is thought to be due to diurnal variations in intradiscal water, proteoglycan, and sodium ion concentration.

Omalizumab is effective for a patient with pollen-food allergy syndrome who experienced intractable lip edema.

Pollen-food allergy syndrome (PFAS) is an immunoglobulin E (IgE)-mediated allergic reaction caused when patients with pollen allergy ingest food having cross-reactivity with pollen. To date, no effective treatment method for this has been established. Here we report the case of a patient with PFAS who experienced lip edema, causing difficulties in treatment. This report describes the case of a 12-year-old boy with perennial allergic rhinitis since the age of 8 years. After ingesting fresh fruits and raw vegetables at the age of 11 years, he started to experience lip edema repeatedly. Thus, the patient was referred to our department. Based on the results of serum antigen-specific IgE, prick-to-prick, and allergen component tests, he was diagnosed with PFAS. He has been instructed to avoid causative food. Furthermore, the treatment using an antihistamine and antileukotriene receptor antagonist was initiated for pollen allergy. Sublingual immunotherapy (SLIT) for Japanese cedar pollen was initiated because the patient experienced severe nasal allergy symptoms during the dispersal season of this pollen. These treatments alleviated the nasal symptoms; however, the lip edema persisted. Omalizumab administration improved the lip edema. The combination of SLIT and omalizumab may be an effective treatment option for patients with PFAS.

Metastasis of Primary Cutaneous Adenoid Cystic Carcinoma to the Nasal Septum after 17 years: A Case Report.

Primary cutaneous adenoid cystic carcinoma (PCACC) is extremely rare, and although distant metastasis has been reported, to date, there are no reports regarding metastasis to the nasal septum. We report a rare case of PCACC that metastasized to the nasal septum 17 years after the first surgery in a 59-year-old woman. She initially presented with a mass under the skin of her left mammary papilla. After a biopsy revealed the presence of an adenoid cystic carcinoma, the tumor was excised and definitively diagnosed as a PCACC. Five years after surgery, the patient presented with left lung metastasis and underwent a partial resection of the left lung. However, 8 years after this procedure, the patient had to undergo a partial resection of the right lung because of right lung metastasis. Four years thereafter, the patient presented with nasal septal metastasis. The tumor was excised successfully using a combined technique integrating intranasal and extranasal approaches. The patient is currently undergoing regular follow-up tests. Thus, in such cases, lifelong follow-up is necessary while checking for both distant metastasis and instances of local recurrence.

Long-term sublingual immunotherapy provides better effects for patients with Japanese cedar pollinosis.

OBJECTIVE: Japanese cedar pollinosis is an endemic disease affecting a large proportion of Japan's population. Five seasons have passed since sublingual immunotherapy (SLIT) for Japanese cedar pollinosis was included in the public insurance coverage in Japan. In this study, we evaluated the clinical effects of long-term SLIT for Japanese cedar pollinosis on upper respiratory symptoms primarily represented by nasal symptoms and inflammation of the respiratory tract in the 2019 season, in which considerable amount of cedar pollen was dispersed. METHODS: This study involved 95 patients who were undergoing SLIT for Japanese cedar pollinosis after the initiation at some point between 2014 and 2018, and this group of patients was compared with a control group comprising 21 patients receiving preseasonal prophylactic treatment (with a second-generation antihistaminic drug). We evaluated the patients' nasal/eye symptoms, total nasal symptom and medication score (TNSMS), and quality of life according to relevant guidelines. In addition, the levels of peripheral blood eosinophils, serum total IgE, Japanese cedar antigen-specific IgE, Cryj1-specific IgG4, and fractional exhaled nitric oxide (FENO) were measured as objective indices. RESULTS: From the fourth season (SLIT4), nasal discharge, sneezing, nasal obstruction symptoms, and TNSMS significantly decreased compared with those in the preseasonal prophylactic treatment and SLIT1 groups. In the patients suspected to have eosinophilic airway inflammation (with a baseline FENO ≥25 ppb), the interannual variability of FENO levels significantly reduced after 5 years of treatment. CONCLUSION: The efficacy of SLIT was noted from the first year of treatment, even in a year when pollen profusely dispersed. Thus, long-term continuous treatment with SLIT may alleviate nasal symptoms as well as eosinophilic airway inflammation.

Structural changes in female-to-male sex-reversing gonads of Rana RUGOSA.

The phenotypic sex of many species of amphibians is subject to reversal by steroid hormones. The mechanism of this process, however, still remains largely unknown. As a step toward understanding the histological changes during sex reversal in amphibians, we analyzed two- and three-dimensional (2D and 3D) structures of sex-reversing gonads in Rana rugosa frogs. 2D views revealed that many oocytes in the wild-type ovary disappeared during female-to-male sex-reversal concomitant with the emergence of Vasa-positive small germ cells. Some of the germ cells were labeled with BrdU. BrdU-positive germ cells were few in the testosterone (T) treated ovaries at days 8 and 16, which resembled wild-type ovaries. Basement membranes became disrupted by day 24 in T-treated ovaries. However, the membranes were later reconfigured into testis-like gonadal structures 40 days after T treatment. 3D imaging of the sex-reversing gonad using serial immunostained sections showed that germ cells were organized in linear fashion extending out from where the sex-reversing gonad attached to the mesorchium 24 days after T treatment. Germ cells were increased in number by 40 days and were localized to the cortex of the gonads. In a T-untreated testis at day 24, many germ cells were distributed throughout the cortex except in the central space, while the efferent duct ran between two sheets of the mesorchium. These results, taken together, suggest that the mesorchium plays an important role in the organization of testicular structure. This is the first report showing germ cell ontogeny and organization in the female-to-male sex-reversing gonad in a vertebrate species.

Molecular cloning and characterization of anti-Müllerian hormone (AMH) from the Japanese wrinkled frog, Rana rugosa.

The role of anti-Müllerian hormone (AMH) during gonad development has been studied extensively in many species of mammal, bird, reptile, and fish but remains unresolved in amphibians. In male mammalian embryos, Sox9 activates AMH expression, which initiates regression of the Müllerian ducts. However, Sox9 (Sry-related HMG box 9) is unlikely to initiate AMH in chicken, because AMH precedes Sox9 expression in this species. To clarify whether AMH is involved in testicular differentiation in amphibians, we cloned the full-length AMH cDNA from the Japanese wrinkled frog, Rana rugosa. The AMH gene, which appears to be autosomal, is exclusively expressed in the testis of adult frog among 8 different tissues examined; Sertoli cells are probably responsible for its expression. AMH expression was found in the undifferentiated gonad of both male and female tadpoles, increasing in the differentiating testis. Moreover, we observed consensus binding sites for Sox9 in the 5'-flanking region of the AMH gene. Sox9 stimulated statistically significant AMH expression in luciferase reporter assays when coexpressed in Xenopus kidney-derived A6 cells. However, Sox9 expression showed no sexual dimorphism when AMH expression was up-regulated in the developing testis. These results, taken together, suggest that AMH is probably involved in testicular differentiation in R. rugosa, although an additional, perhaps tissue-specific, transcription factor may be required for the regulation of AMH transcription.