The Potentiality of Natural Products and Herbal Medicine as Novel Medications for Parkinson's Disease: A Promising Therapeutic Approach.

As the global population ages, the prevalence of Parkinson's disease (PD) is steadily on the rise. PD demonstrates chronic and progressive characteristics, and many cases can transition into dementia. This increases societal and economic burdens, emphasizing the need to find effective treatments. Among the widely recognized causes of PD is the abnormal accumulation of proteins, and autophagy dysfunction accelerates this accumulation. The resultant Lewy bodies are also commonly found in Alzheimer's disease patients, suggesting an increased potential for the onset of dementia. Additionally, the production of free radicals due to mitochondrial dysfunction contributes to neuronal damage and degeneration. The activation of astrocytes and the M1 phenotype of microglia promote damage to dopamine neurons. The drugs currently used for PD only delay the clinical progression and exacerbation of the disease without targeting its root cause, and come with various side effects. Thus, there is a demand for treatments with fewer side effects, with much potential offered by natural products. In this study, we reviewed a total of 14 articles related to herbal medicines and natural products and investigated their relevance to possible PD treatment. The results showed that the reviewed herbal medicines and natural products are effective against lysosomal disorder, mitochondrial dysfunction, and inflammation, key mechanisms underlying PD. Therefore, natural products and herbal medicines can reduce neurotoxicity and might improve both motor and non-motor symptoms associated with PD. Furthermore, these products, with their multi-target effects, enhance bioavailability, inhibit antibiotic resistance, and might additionally eliminate side effects, making them good alternative therapies for PD treatment.

Breast Reconstruction after Breast Implant-Associated Anaplastic Large Cell Lymphoma Treatment: A Case Report and Literature Review.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a T-cell non-Hodgkin's lymphoma that occurs in patients with at least one prior textured breast implant. BIA-ALCL has a relatively good prognosis when treated promptly. However, data on the methods and timing of the reconstruction process are lacking. Herein, we report the first case of BIA-ALCL in Republic of Korea in a patient who underwent breast reconstruction using implants and an acellular dermal matrix (ADM). A 47-year-old female patient was diagnosed with BIA-ALCL stage IIA (T4N0M0) and underwent bilateral breast augmentation using textured breast implants. She then underwent removal of both breast implants, total bilateral capsulectomy, adjuvant chemotherapy, and radiotherapy. There was no evidence of recurrence at 28 months postoperatively; therefore, the patient wished to undergo breast reconstruction surgery. A smooth surface implant was used to consider the patient's desired breast volume and body mass index. The right breast was reconstructed with a smooth surface implant and an ADM in the prepectoral plane. Breast augmentation was performed on the left breast using a smooth surface implant. The patient was satisfied with the results and recovered fully with no complications.

Multiple low-dose radiation-induced neuronal cysteine transporter expression and oxidative stress are rescued by N-acetylcysteine in neuronal SH-SY5Y cells.

Recently, several studies have demonstrated that low-dose radiation (LDR) therapy has positively impacts on the treatment of Alzheimer's disease (AD). LDR suppresses the production of pro-neuroinflammation molecules and improves cognitive function in AD. However, it is unclear whether direct exposure to LDR causes beneficial effects and what mechanism is involved in neuronal cells. In this study, we first determined the effect of high-dose radiation (HDR) alone on C6 cells and SH-SY5Y cells. We found that SH-SY5Y cells were more vulnerable than C6 cells to HDR. Moreover, in neuronal SH-SY5Y cells exposed to single or multiple LDR, N-type cells showed decreased cell viability with increasing radiation exposure time and frequency, but S-type cells were unaffected. Multiple LDR increased proapoptotic molecules such as p53, Bax and cleaved caspase-3, and decreased anti-apoptotic molecule (Bcl2). Multiple LDR also generated free radicals in neuronal SH-SY5Y cells. We detected a change in the expression of the neuronal cysteine transporter EAAC1. Pretreatment with N-acetylcysteine (NAC) rescued the increased in EAAC1 expression and the generation of ROS in neuronal SH-SY5Y cells after multiple LDR. Furthermore, we verified whether the increased in EAAC1 expression induces cell defense or cell death promotion signaling. We showed that transient overexpression of EAAC1 reduced the multiple LDR-induced p53 overexpression in neuronal SH-SY5Y cells. Our results indicate that neuronal cells can be injured by increased production of ROS not only by HDR but also by multiple LDR, which suggests that combination treatment with anti-free radical agents such as NAC may be useful in multiple LDR therapy.

Improvement Effect of Soyeom Pharmacopuncture on Gout via NLRP3 Inflammasome Regulation.

Objectives: Gout is an inflammatory arthritis of the joints and soft tissues occurring due to deposition of monosodium urate (MSU) crystals, which are caused by persistent hyperuricemia. Soyeom pharmacopuncture is one treatment method that has been traditionally used for pain management in Oriental medicine. However, studies on its effect in reducing gout pain have been insufficient. Therefore, we selected Soyeom pharmacopuncture among natural products used in Korea as the new target of our study. Methods: The effects of Soyeom pharmacopuncture were examined in mouse models of acute gout induced by injection of MSU crystals into footpads. IL-1ß, IL-6, and TNF-α production were examined by immunoblotting and enzyme-linked immunosorbent assay as hallmarks of NLRP3 inflammasome and cytokine activation. Results: Soyeom pharmacopuncture reduced foot edema in gout-induced mice, as well as IL-1ß, nitrite, IL-6, and TNF-α production. Moreover, Soyeom pharmacopuncture also reduced MSU-induced gout inflammatory gene expressions, specifically those in the NF-kB pathway. Conclusion: Pharmacopuncture may serve as a new solution for other inflammatory diseases as well. Through active follow-up studies, we could thoroughly understand the clinical value of Soyeom pharmacopuncture.

Effect of Phlorofucofuroeckol A and Dieckol Extracted from Ecklonia cava on Noise-induced Hearing Loss in a Mouse Model.

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

A Novel Treatment Strategy by Natural Products in NLRP3 Inflammasome-Mediated Neuroinflammation in Alzheimer's and Parkinson's Disease.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases. Many studies have demonstrated that the release of NLRP3 inflammasome-mediated proinflammatory cytokines by the excessive activation of microglia is associated with the pathogenesis of AD and PD and suggested that the NLRP3 inflammasome plays an important role in AD and PD development. In both diseases, various stimuli, such as Aß and α-synuclein, accelerate the formation of the NLRP3 inflammasome in microglia and induce pyroptosis through the expression of interleukin (IL)-1ß, caspase-1, etc., where neuroinflammation contributes to gradual progression and deterioration. However, despite intensive research, the exact function and regulation of the NLRP3 inflammasome has not yet been clearly identified. Moreover, there have not yet been any experiments of clinical use, although many studies have recently been conducted to improve treatment of inflammatory diseases using various inhibitors for NLRP3 inflammasome pathways. However, recent studies have reported that various natural products show improvement effects in the in vivo models of AD and PD through the regulation of NLRP3 inflammasome assembly. Therefore, the present review provides an overview of natural extraction studies aimed at the prevention or treatment of NLRP3 inflammasome-mediated neurological disorders. It is suggested that the discovery and development of these various natural products could be a potential strategy for NLRP3 inflammasome-mediated AD and PD treatment.

Aqueous extract of Chrysanthemum morifolium Ramat. inhibits RANKL-induced osteoclast differentiation by suppressing the c-fos/NFATc1 pathway.

OBJECTIVE: The flower of chrysanthemum, used worldwide as a medicinal and edible product, has shown various bioactivities, such as anti-inflammatory, antioxidant, anti-tumorigenic, and hepatoprotective activities, as well as cardiovascular protection. However, the effect of Chrysanthemum morifolium Ramat. on the regulation of osteoclast differentiation has not yet been reported. In this study, we aimed to investigate the inhibitory effect of Chrysanthemum morifolium Ramat. water extract (CME) on RANKL-induced osteoclast differentiation in mouse bone marrow-derived macrophages (BMMs). STUDY DESIGN: Bone marrow-derived macrophages (BMMs) isolated from the C57BL/6 J mice. The viability of BMMs was detected with MTT assays. Inhibitory effects of CME on osteoclast differentiation and bone resorption was measured by TRAP staining and Pit assay. Osteoclast differentiation-associated gene expression were assessed by Real-time quantitative polymerase chain reaction. Intracellular signaling molecules was assessed by western blot. RESULTS: CME significantly inhibited osteoclast differentiation in BMMs without cytotoxicity, besides inhibiting MAPK/c-fos and PLCγ2/CREB activation. The inhibitory effects of CME on differentiation-related signaling molecules resulted in significant repression of NFATc1 expression, which is a key transcription factor in osteoclast differentiation, fusion, and activation. CONCLUSION: Our results confirmed the inhibition of RANKL-induced PLCγ2/CREB/c-fos/NFATc1 activation by CME during osteoclast differentiation. The findings collectively suggested CME as a traditional therapeutic agent for osteoporosis, RA, and periodontitis.

Effect of age on the gap-prepulse inhibition of the cortical N1-P2 complex in humans as a step towards an objective measure of tinnitus.

The gap-prepulse inhibition of the acoustic startle reflex has been widely used as a behavioral method for tinnitus screening in animal studies. The cortical-evoked potential gap-induced inhibition has also been investigated in animals as well as in human subjects. The present study aimed to investigate the effect of age on the cortical N1-P2 complex in the gap-prepulse inhibition paradigm. Fifty-seven subjects, aged 20 to 68 years, without continuous tinnitus, were tested with two effective gap conditions (embedded gap of 50- or 20-ms duration). Retest sessions were performed within one month. A significant gap-induced inhibition of the N1-P2 complex was found in both gap durations. Age differently affected the inhibition, depending on gap duration. With a 50-ms gap, the inhibition decreased significantly with the increase in age. This age-inhibition relationship was not found when using a 20-ms gap. The results were reproducible in the retest session. Our findings suggest that the interaction between age and gap duration should be considered when applying the gap-induced inhibition of the cortical-evoked potential as an objective measure of tinnitus in human subjects. Further studies with tinnitus patients are warranted to identify gap duration that would minimize the effects of age and maximize the difference in the inhibition between those with and without tinnitus.

Incidence and Mortality Rates of Thoracic Aortic Dissection in Korea - Inferred from the Nationwide Health Insurance Claims.

BACKGROUND: Aortic dissection (AD) is one of the most catastrophic diseases and is associated with high morbidity and mortality. The aim of this study is to investigate the hospital incidence and mortality rates of thoracic AD in Korea using a nationwide database. METHODS: We conducted a nationwide population-based study using the health claims data of the National Health Insurance Service in Korea. From 2005 to 2016, adult patients newly diagnosed with AD were included. All patients were divided into the following four subgroups by treatment: type A surgical repair (TASR), type B surgical repair (TBSR), thoracic endovascular aortic repair (TEVAR), and medical management (MM). The incidence rate, mortality rate, and risk factors of in-hospital mortality were evaluated. RESULTS: In total, 18,565 patients were newly diagnosed with AD (TASR, n = 4,319 [23.3%]; TBSR, n = 186 [1.0%]; TEVAR, n = 697 [3.8%]; MM, n = 13,363 [72.0%]). The overall AD incidence rate was 3.76 per 100,000 person-years and exhibited a gradual increase during the study period (3.29 to 4.82, P < 0.001). The overall in-hospital mortality rate was 10.84% and remained consistent (P = 0.57). However, the in-hospital mortality rate decreased in the TASR subgroup (18.23 to 11.27%, P = 0.046). An older age, the female sex, hypertension, and chronic kidney disease were independent risk factors for in-hospital mortality. CONCLUSION: The incidence of thoracic AD has gradually increased in Korea. The in-hospital mortality in the TASR subgroup decreased over the decade, although the overall mortality of AD patients did not change.

Reproducible Large-Scale Isolation of Exosomes from Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells and Their Application in Acute Kidney Injury.

Acute kidney injury (AKI) is a fatal medical episode caused by sudden kidney damage or failure, leading to the death of patients within a few hours or days. Previous studies demonstrated that exosomes derived from various mesenchymal stem/stromal cells (MSC-exosomes) have positive effects on renal injuries in multiple experimental animal models of kidney diseases including AKI. However, the mass production of exosomes is a challenge not only in preclinical studies with large animals but also for successful clinical applications. In this respect, tangential flow filtration (TFF) is suitable for good manufacturing practice (GMP)-compliant large-scale production of high-quality exosomes. Until now, no studies have been reported on the use of TFF, but rather ultracentrifugation has been almost exclusively used, to isolate exosomes for AKI therapeutic application in preclinical studies. Here, we demonstrated the reproducible large-scale production of exosomes derived from adipose tissue-derived MSC (ASC-exosomes) using TFF and the lifesaving effect of the ASC-exosomes in a lethal model of cisplatin-induced rat AKI. Our results suggest the possibility of large-scale stable production of ASC-exosomes without loss of function and their successful application in life-threatening diseases.

Prognostic value of mismatch repair deficiency in patients with advanced gastric cancer, treated by surgery and adjuvant 5-fluorouracil and leucovorin chemoradiotherapy.

OBJECTIVE: The predictive value of mismatch repair protein deficiency (MMRD) for chemoradiotherapeutic outcome has rarely been reported in gastric cancer. This study investigated the clinical significance of MMRD as a prognostic factor for tumor recurrence, and as a predictor of response to adjuvant chemoradiotherapy in advanced gastric cancer patients. METHODS: Between 1995 and 2008, tissue specimens of 881 patients who underwent radical gastrectomy for stage II and III gastric cancer were analyzed. MMRD was assessed using immunohistochemical stains for MLH1, PMS2, MSH2, and MSH6. Patients were divided into two groups according to adjuvant treatment: a 5-fluorouracil/leucovorin (FL) adjuvant chemoradiotherapy group and a surgery alone group. Disease-free survival (DFS) was compared between the two groups correlated to MMRD. Risk factors for tumor recurrence were analyzed using multivariate analysis. RESULTS: Of the 881 gastric cancer patients, 88 (10.0%) exhibited MMRD and 398 (45.2%) patients received adjuvant FL chemoradiotherapy. The multivariate analysis revealed that MMRD was a good independent prognostic factor (hazard ratio, 0.572; 95% confidence interval, 0.370-0.883; P = 0.012). For stage III gastric cancer displaying mismatch repair protein proficiency (MMRP), adjuvant FL chemoradiotherapy after surgery resulted in better DFS than surgery alone (P = 0.001). Among the stage II gastric cancer patients, adjuvant FL chemoradiotherapy did not show survival benefit, regardless of MMRD. CONCLUSION: MMRD is a good independent prognostic factor in advanced gastric cancer. Adjuvant FL chemoradiotherapy was beneficial in patients with stage III gastric cancer with MMRP but not in those with MMRD.

Coffee intake and decreased amyloid pathology in human brain.

Several epidemiological and preclinical studies supported the protective effect of coffee on Alzheimer's disease (AD). However, it is still unknown whether coffee is specifically related with reduced brain AD pathologies in human. Hence, this study aims to investigate relationships between coffee intake and in vivo AD pathologies, including cerebral beta-amyloid (Aß) deposition, the neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMH). A total of 411 non-demented older adults were included. Participants underwent comprehensive clinical assessment and multimodal neuroimaging including [11C] Pittsburgh compound B-positron emission tomography (PET), [18F] fluorodeoxyglucose PET, and magnetic resonance imaging scans. Lifetime and current coffee intake were categorized as follows: no coffee or <2 cups/day (reference category) and ≥2 cups/day (higher coffee intake). Lifetime coffee intake of ≥2 cups/day was significantly associated with a lower Aß positivity compared to coffee intake of <2 cups/day, even after controlling for potential confounders. In contrast, neither lifetime nor current coffee intake was not related to hypometabolism, atrophy of AD-signature region, and WMH volume. The findings suggest that higher lifetime coffee intake may contribute to lowering the risk of AD or related cognitive decline by reducing pathological cerebral amyloid deposition.

Regulation of p21 expression for anti-apoptotic activity of DDX3 against sanguinarine-induced cell death on intrinsic pathway.

BACKGROUND: DDX3 plays a role in multicellular pathways, especially exerting an anti-apoptotic effect on extrinsic apoptosis. However, studies on the role of DDX3 in intrinsic apoptosis are lacking. PURPOSE: In this study, we aimed to study the bio-function of DDX3 anti-apoptotic activity in the intrinsic pathway using HeLa cells treated with sanguinarine. STUDY DESIGN: Screening of apoptosis-inducing agents found that sanguinarine was the most effective. After treatment with sanguinarine, cell viability, caspase-3 activity, and intrinsic gene expression were analyzed. FACS assays were used to analyze the effect of overexpression and knockdown of DDX3 to determine its role on intrinsic apoptosis. The relationship between DDX3 and the inhibition of p21 and apoptosis was investigated. RESULTS: Sanguinarine was determined to be the most effective intrinsic apoptosis-inducing agent in HeLa cervical cancer cells. DDX3 upregulated anti-apoptotic gene expression (Bcl-xL, cyclin D1, cyclin E, and cyclin B1) and downregulated pro-apoptotic gene expression (caspase-3, Bax) after sanguinarine treatment. The apoptotic cell death rate increased from 8.74% (sanguinarine-treated control) to 17.6% after the knockdown of DDX3 but decreased to 5.29% after DDX3 overexpression. The results implied that p21 might be involved in the toxicity of sanguinarine to HeLa cells. Overexpression and knockdown of DDX3 under sanguinarine-treated conditions showed that DDX3 inhibited p21 expression in sanguinarine-treated HeLa cells. Notably, when we tested p21 expression among eight mutants located in the functional residues of DDX3 (S90A, S90E, T204A, T204E, GET, NEAD, LAT, and HRISR) under sanguinarine-treated conditions, only the S90E mutation in DDX3 had an effect on the inhibition of p21 expression and levels of pro-apoptotic genes (Bax and caspase-3) and anti-apoptotic genes (Bcl-xL, cyclin D1, cyclin E, and cyclin B1), as well as DDX3. CONCLUSION: Taken together, the results suggest that the S90E residue is important for the regulation of p21 expression responsible for the anti-apoptotic activity of DDX3 in HeLa cells treated with sanguinarine. A model of the antiapoptotic function of DDX3 on sanguinarine-treated HeLa cells was proposed to understand the molecular mechanism of the intrinsic apoptosis inhibition in cervical cancer cells.

Direct Three-Dimensional Observation of Core/Shell-Structured Quantum Dots with a Composition-Competitive Gradient.

Synthesizing semiconductor nanoparticles through core/shell structuring is an effective strategy to promote the functional, physical, and kinetic performance of optoelectronic materials. However, elucidating the internal structure and related atomic distribution of core/shell structured quantum dots (QDs) in three dimensions, particularly at heterostructure interfaces, has been an overarching challenge. Herein, by applying complementary analytical techniques of electron microscopy and atom probe tomography, the dimensional, structural, topological, and compositional information on commercially available 11.8 nm-sized CdSSe/ZnS QDs were obtained. Systematic experiments at high resolution reveal the presence of a 1.8 nm-thick Cd xZn1 - xS inner shell with a composition gradient between the CdSe core and the ZnS outermost shell. More strikingly, the inner shell shows compositional variation because of competitive atomic configuration between Cd and ZnS, but it structurally retains a zinc-blende crystal structure with the core. The inner shell may grow through the decreased reactivity of S with Cd, followed by atomic diffusion-related processes. The composition-competitive gradient inner shell alleviates lattice misfit strain at heterostructure interfaces, thereby enhancing the quantum yield and photostabilty to a greater extent than those of other single-shell structures. Thus, this precise measurement approach could offer a potential pathway to develop a wide variety of three-dimensional core/shell-structured materials.

Association of Coffee Consumption with Hearing and Tinnitus Based on a National Population-Based Survey.

Coffee is the one of the most common beverages worldwide and has received considerable attention for its beneficial health effects. However, the association of coffee with hearing and tinnitus has not been well studied. The aim of this study was to investigate the association of coffee with hearing and tinnitus based on a national population-based survey. We evaluated hearing and tinnitus data from the 2009⁻2012 Korean National Health and Nutrition Examination Survey and their relationship with a coffee consumption survey. All patients underwent a medical interview, physical examination, hearing test, tinnitus questionnaire and nutrition examination. Multivariable logistic regression models were used to examine the associations between coffee and hearing loss or tinnitus. We evaluated 13,448 participants (≥19 years) participants. The frequency of coffee consumption had a statistically significant inverse correlation with bilateral hearing loss in the 40⁻64 years age group. Daily coffee consumers had 50⁻70% less hearing loss than rare coffee consumers, which tended to be a dose-dependent relationship. In addition, the frequency of coffee consumption had an inverse correlation with tinnitus in the 19⁻64 years age group but its association was related with hearing. Brewed coffee had more of an association than instant or canned coffee in the 40⁻64 years age group. These results suggest a protective effect of coffee on hearing loss and tinnitus.

Complete genome sequence of Flavobacterium kingsejongi WV39, a type species of the genus Flavobacterium and a microbial C40 carotenoid zeaxanthin producer.

A novel species, Flavobacterium kingsejongi WV39, isolated from feces of Antarctic penguins and a type species of the genus Flavobacterium, is yellow because it synthesizes a C40 carotenoid zeaxanthin. The complete genome of F. kingsejongi WV39 is made up of a single circular chromosome (4,224,053bp, 39.8% G+C content). Annotation analysis revealed 3,955 coding sequences, 72 RNAs (18 rRNA+54 tRNA), and five genes involved in zeaxanthin biosynthesis. The key gene encoding ß-carotenoid hydroxylase (CrtZ), which is the last enzyme in the zeaxanthin biosynthetic pathway, was cloned and subjected to complementary analysis in a heterologous E. coli strain. The CrtZ of F. kingsejongi WV39 showed a higher activity than other reported CrtZs.

Removal of non-aqueous phase liquids (NAPLs) from TPH-saturated sandy aquifer sediments using in situ air sparging combined with soil vapor extraction.

Contamination in coastal aquifer plains is of great concern in many countries given that non-aqueous phase liquids (NAPLs) have polluted numerous sites through accidental oil spills or improper disposal. We have developed a method to remove pollutants such as NAPLs from sandy sediment samples collected from the Mandol area of Gomso Bay in western South Korea. The sediments were collected from around the diffuser in a two-dimensional (2D) acrylic reaction apparatus, and these contained a total petroleum hydrocarbon (TPH) concentration of 89.3 ppm (mg/kg media). The maximum perchloroethylene (PCE) concentration was 398.51 ppm in the unsaturated zone and 0.77 ppm in the saturated zone. Volatile organic compounds (VOCs) were detected between 20 and 44 hour. However, non-volatile contaminants remained in the sediments after treatment. In situ air sparging (IAS) combined with soil vapor extraction (SVE), transformation from sorbed and nonaqueous phases to the vapor phase, is incomplete when treatment is performed using a pervasive air flow for sediments such as the sand of Mandol. During air transformation, the groundwater flow conditions increased the rate of contaminant removal. Although pilot-scale testing in the field site was fluctuated due to the heterogeneous of sediments condition, this 2D study found that the proposed method can alter the measurable geophysical properties of NAPLs. These findings demonstrate that IAS combined with SVE in the saturated zone is an effective technology for aquifer remediation high applicability of sandy coastal sediments contaminated by NAPLs.

Deep Learning-Based Survival Analysis Identified Associations Between Molecular Subtype and Optimal Adjuvant Treatment of Patients With Gastric Cancer.

PURPOSE: Gastric cancer (GC) is the third-leading cause of cancer-related deaths. Several pivotal clinical trials of adjuvant treatments were performed during the previous decade; however, the optimal regimen for adjuvant treatment of GC remains controversial. PATIENTS AND METHODS: We developed a novel deep learning-based survival model (survival recurrent network [SRN]) in patients with GC by including all available clinical and pathologic data and treatment regimens. This model uses time-sequential data only in the training step, and upon being trained, it receives the initial data from the first visit and then sequentially predicts the outcome at each time point until it reaches 5 years. In total, 1,190 patients from three cohorts (the Asian Cancer Research Group cohort, n = 300; the fluorouracil, leucovorin, and radiotherapy cohort, n = 432; and the Adjuvant Chemoradiation Therapy in Stomach Cancer cohort, n = 458) were included in the analysis. In addition, we added Asian Cancer Research Group molecular classifications into the prediction model. SRN simulated the sequential learning process of clinicians in the outpatient clinic using a recurrent neural network and time-sequential outcome data. RESULTS: The mean area under the receiver operating characteristics curve was 0.92 ± 0.049 at the fifth year. The SRN demonstrated that GC with a mesenchymal subtype should elicit a more risk-adapted postoperative treatment strategy as a result of its high recurrence rate. In addition, the SRN found that GCs with microsatellite instability and GCs of the papillary type exhibited significantly more favorable survival outcomes after capecitabine plus cisplatin chemotherapy alone. CONCLUSION: Our SRN predicted survival at a high rate, reaching 92% at postoperative year 5. Our findings suggest that SRN-based clinical trials or risk-adapted adjuvant trials could be considered for patients with GC to investigate more individualized adjuvant treatments after curative gastrectomy.

A Molecular Basis for the Inhibition of Transient Receptor Potential Vanilloid Type 1 by Gomisin A.

Transient receptor potential (TRP) channel has critical actions as conditional sensors in primary afferent neurons. We studied the regulatory action of gomisin A on TRPV1 channel current in this report. Schisandra chinensis contains bioactive compounds such as the gomisin derivatives and their related compounds. Coapplication with gomisin A inhibited the capsaicin-mediated inward peak current. This inhibitory effect of gomisin A on capsaicin-induced inward current showed concentration-dependence and was reversible. The half maximal inhibitory concentration of gomisin A was 62.7 ± 8.4 µM. In addition, this inhibition occurred in a noncompetition regulation mode and voltage insensitive manner. Furthermore, molecular docking studies of gomisin A on TRPV1 showed that it interacted predominantly with residues at cavities in the segments 1 and 2 of each subunit. Four potential binding sites for this ligand in the extracellular region at sensor domain of TRPV1 channel were identified. Point mutagenesis studies were undertaken, and gomisin A potency decreased for both the Y453A and N467A mutants. The double mutation of Y453 and N467 significantly attenuated inhibitory effects by gomisin A. In summary, this study revealed the molecular basis for the interaction between TRPV1 and gomisin A and provides a novel potent interaction ligand.

Fat Graft Survival After Recipient Site Pretreatment With Fractional Carbon Dioxide Laser.

BACKGROUND: Fat grafting is a commonly performed procedure not only for augmenting the soft tissue but also for regeneration in esthetic and reconstructive plastic surgery.However, unpredictable fat survival rate because of high resorption rate is remained as the main problem. The purpose of this study was to investigate the effect of pretreatment of the recipient site to the fat survival using fractional carbon dioxide (CO2) laser. METHODS: The rats were divided to 2 groups. Inguinal fat pads of rats were transplanted to the dorsum without pretreatment in the control group. The study group was preconditioned by fractional CO2 laser to the recipient site 1 week before fat graft.The pulse energy was set to 100 mJ. Transplanted fat tissues were harvested at postoperative days 1, 3, 7, 14, and 28 and were analyzed morphologically, histologically, and immunohistochemically. RESULTS: Weight and volume in the control group was more decreased than in the study group at postoperative day 28. Histological evaluation showed less inflammation, less fibrosis, less vacuolization, and better integrity of adipocytes. Immunohistologically, microvessel density in the study group was higher than in the control group (P < 0.05) at postoperative day 1. Survival rate in the study group was higher than in the control group at postoperative days 1, 3, 7, and 14 (P < 0.05). CONCLUSIONS: Pretreatment of recipient site using fractional CO2 laser helped vascularization in the early stage in fat graft and solved the ischemic condition, so it improved fat survival rate.