Adult cancer patients' barriers to and satisfaction with care at a National Cancer Hospital in Vietnam.

STUDY OBJECTIVE: This study assessed the overall satisfaction with oncological care, including barriers to care, and identified its associated predictors among adult cancer patients in Vietnam. METHODS: In this cross-sectional study, we enrolled 300 adult cancer patients receiving inpatient care at a large urban oncological hospital between June and July 2022. Multivariable linear regression analyses examined associations between patient experiences and overall satisfaction ratings with cancer care. RESULTS: The mean overall satisfaction with oncological care was 8.82 out of 10, with 98.0% recommending this facility to their friends and family. In an adjusted model, being female (ß = 0.29, 95%CI: 0.04, 0.53), endorsing satisfaction with patient-nurse communication (ß = 0.33, 95%CI: 0.13, 0.53), patient-doctor communication (ß = 0.40, 95%CI: 0.11, 0.70), and psychoeducation about oncological medication management (ß = 0.30, 95%CI: 0.14, 0.45) were positively associated with overall ratings. In contrast, individuals with delays in treatment scheduling reported lower overall satisfaction with oncological care (ß = -0.38, 95%CI: -0.64, -0.13). Patients perceived health system, social/environmental, and individual barriers to care: worries about income loss due to attending treatment (43.3%); fear, depression, anxiety, and distress (36.8%); concerns about affordability of treatment (36.7%) and transportation problems (36.7%); and excessive waiting times for appointments (28.8%). CONCLUSION: This study showed high overall patient satisfaction with cancer care quality. Patient-centered communication strategies and psychoeducation about oncological medication management may be targeted to further enhance the cancer inpatient experience. Raising awareness about treatment options and services, and integrating mental health awareness into oncological care may ameliorate patient distress and facilitate greater satisfaction with oncological treatment processes.

The relationship between HIV-related stigma and quality of life among HIV infected outpatients: A cross-sectional study in Vietnam.

Background: The impact of stigma on individuals with HIV remains a significant challenge, causing feelings of worthlessness, shame, and emotional distress. This study aimed to examine the relationship between HIV-related stigma and quality of life (QOL) among HIV-infected outpatients initiating antiretroviral therapy (ART) in Vietnam. Design and methods: This was a cross-sectional study which conducted at Vinh General Hospital, Nghe An Province, involved 323 HIV-infected outpatients. Participants were surveyed between October 2020 and October 2021. The study collected data through structured interviews, assessing socio-demographic factors, HIV stigma, and QOL. Results: The result showed that HIV-infected outpatients experiencing higher stigma showed poorer QOL across various domains. The negative impact of stigma was particularly evident in domains related to physical health, psychological well-being, and spirituality. Participants who were married, had children, consumed alcohol, had comorbidities (particularly hepatitis B/C), and lacked a history of drug use reported varying levels of correlation with QOL domains and stigma. Conclusions: By identifying the intricate connections between stigma and QOL, the study provides valuable insights for designing comprehensive interventions that prioritize the well-being of HIV infected outpatients.

CRISPR/Cas9 targeted mutations of OsDSG1 gene enhanced salt tolerance in rice.

Salinization is one of the leading causes of arable land shrinkage and rice yield decline, recently. Therefore, developing and utilizing salt-tolerant rice varieties have been seen as a crucial and urgent strategy to reduce the effects of saline intrusion and protect food security worldwide. In the current study, the CRISPR/Cas9 system was utilized to induce targeted mutations in the coding sequence of the OsDSG1, a gene involved in the ubiquitination pathway and the regulation of biochemical reactions in rice. The CRISPR/Cas9-induced mutations of the OsDSG1 were generated in a local rice cultivar and the mutant inheritance was validated at different generations. The OsDSG1 mutant lines showed an enhancement in salt tolerance compared to wild type plants at both germination and seedling stages indicated by increases in plant height, root length, and total fresh weight as well as the total chlorophyll and relative water contents under the salt stress condition. In addition, lower proline and MDA contents were observed in mutant rice as compared to wild type plants in the presence of salt stress. Importantly, no effect on seed germination and plant growth parameters was recorded in the CRISRP/Cas9-induced mutant rice under the normal condition. This study again indicates the involvement of the OsDSG1 gene in the salt resistant mechanism in rice and provides a potential strategy to enhance the tolerance of local rice varieties to the salt stress.

Microglial inhibition alleviates alpha-synuclein propagation and neurodegeneration in Parkinson's disease mouse model.

The accumulation of alpha-synuclein (αSyn) is widely recognized as the main pathological process in Parkinson's disease (PD). Additionally, neuroinflammation is considered to be one of the contributing mechanisms in the development of PD. In light of this, it is hypothesized that the reactive microglia exacerbate the propagation of αSyn and neurodegeneration, while the inhibition of microglial activity may mitigate these effects. To test this hypothesis, αSyn preformed fibrils (PFF)-injected PD mouse model was employed. Co-injection of lipopolysaccharide (LPS) and PFF was performed to investigate if microglial reactivity intensified αSyn propagation and neurodegeneration. Additionally, oral administration of PLX5622, a microglial inhibitor that targets the colony-stimulating factor 1 receptor, was given for two weeks before and after PFF injection each to explore if microglial inhibition could prevent or reduce αSyn pathology. Intrastriatal co-injection of LPS and PFF resulted in increased microglial reactivity, αSyn accumulation, and neurodegeneration compared to PFF injection alone. However, treatment with PLX5622 significantly suppressed microglial reactivity, reduced αSyn pathology, and alleviated dopaminergic neuron degeneration in the PD mouse model injected with PFF. Based on these findings, it is evident that microglial reactivity plays a crucial role in the progression of αSyn pathology and neurodegeneration in PD. Furthermore, the results suggest that microglial inhibition may hold promise as a therapeutic strategy to delay the progression of αSyn pathology in PD.

The interaction between magnesium intake, the genetic variant INSR rs1799817 and colorectal cancer risk in a Korean population: a case-control study.

Magnesium may have a significant impact on the development of cancer. However, the relationship between magnesium intake and the risk of colorectal cancer (CRC) is unclear. Therefore, we evaluated the association between magnesium intake and the risk of CRC, and we investigated how the insulin receptor (INSR) rs1799817 variant impacts this relationship. Data from 1,420 CRC patients and 2,840 controls from the Korean National Cancer Centre were analysed. A higher intake of magnesium was associated with a reduced risk of CRC in the total population (odds ratio (OR) = 0.65, 95% confidence interval (CI) = 0.52-0.81). We found that G + carriers of INSR rs1799817 with higher magnesium intake had a significantly lower risk of CRC (p for interaction = 0.003). Our findings indicated that high magnesium intake could be associated with a decreased risk of CRC, and this association could be modified by the INSR rs1799817 variant.

Interplay of Zeb2a, Id2a and Batf3 regulates microglia and dendritic cell development in the zebrafish brain.

In vertebrates, the central nervous system (CNS) harbours various immune cells, including parenchymal microglia, perivascular macrophages and dendritic cells, which act in coordination to establish an immune network to regulate neurogenesis and neural function, and to maintain the homeostasis of the CNS. Recent single cell transcriptomic profiling has revealed that the adult zebrafish CNS contains microglia, plasmacytoid dendritic cells (pDCs) and two conventional dendritic cells (cDCs), ccl35+ cDCs and cnn3a+cDCs. However, how these distinct myeloid cells are established in the adult zebrafish CNS remains incompletely defined. Here, we show that the Inhibitor of DNA binding 2a (Id2a) is essential for the development of pDCs and cDCs but is dispensable for the formation of microglia, whereas the Basic leucine zipper transcription factor ATF-like 3 (Batf3) acts downstream of id2a and is required exclusively for the formation of the cnn3a+ cDC subset. In contrast, the Zinc finger E-box-binding homeobox 2a (Zeb2a) promotes the expansion of microglia and inhibits the DC specification, possibly through repressing id2a expression. Our study unravels the genetic networks that govern the development of microglia and brain-associated DCs in the zebrafish CNS.

A stochastic differential equation model for predator-avoidance fish schooling.

This paper presents a mathematical model based on stochastic differential equations (SDEs) to depict the dynamics of a predator-prey system in an aquatic environment characterized by schooling behavior among the prey. The model employs a particle-like approach, incorporating attractive and repulsive forces, akin to phenomena observed in molecular physics, to capture the interactions among the constituent units. Two hunting tactics of the predator, center-attacking and nearest-attacking strategies, are integrated into the model. Numerical simulations of this model unveil four distinct predator-avoidance patterns exhibited by schooling prey: Split and Reunion, Split and Separate into Two Groups, Scattered, and Maintain Formation and Distance. Our results also confirm the effectiveness of large groups of schooling prey in mitigating predation risk, consistent with real-life observations in natural aquatic ecosystems. These findings validate the accuracy and applicability of our model.

Fully Automatized Optimization of Ring-Opening Reactions in Lactone Derivatives via Two-Step Machine Learning.

Cyclization and cycloreversion of organic compounds are fundamental kinetic processes in the design of functional molecules, molecular machines, nanoscale sensors, and switches in the field of molecular and nanoelectronics. We present a fully automatic computational platform for the design of a class of five- and six-membered ring lactones by optimizing the ring-opening reaction rate. Starting from a minimal initial parent set, our algorithm generates iteratively cascades of pools of candidate lactone derivatives where optimization and down-selection are performed without human supervision. We employ the density functional theory combined with the transition state theory to elucidate the exact mechanism leading to the lactone ring-opening reaction. On the basis of the analysis of the reaction pathway and the frontier molecular orbitals, we identify a simple descriptor that can easily correlate with the reaction rate. Consequently, we can omit computationally expensive transition state calculations and deduce the reaction rate from simple ground-state and ionic calculations. To accelerate the platform, we use a data set of the order of 800 molecules to train machine learning models for the prediction of targeted chemical properties, reducing the computational time by a 90% factor. We developed an evolutionary algorithm capable of generating data sets 3 orders of magnitude larger than the initial parent set. Thus, we can explore a large domain of chemical space using minimal computational effort. Our entire platform is modular, and our current implementation for lactone can be further generalized to more complex systems via substitution of the quantum chemical and fingerprinting modules.

Zinc intake, SLC30A8 rs3802177 polymorphism, and colorectal cancer risk in a Korean population: a case-control study.

PURPOSE: Zinc is an essential micronutrient involving in multiple enzymatic reactions of human metabolism and biological functions affecting the cancer development. However, the relationship between dietary zinc intake and colorectal cancer (CRC) risk has been unclear. Herein, our study investigated the relationship between dietary zinc intake and CRC risk, and examined how the SLC30A8 rs3802177 genetic variant affects this association. METHODS: A total of 1431 CRC cases and 2704 controls were selected to investigate the relationship between dietary zinc intake and CRC risk. After excluding individuals without genotype data, 1097 CRC cases and 1559 controls were used to evaluate the interaction between dietary zinc intake and the rs3802177 polymorphism in CRC risk. The odds ratios (ORs) and 95% confidence intervals (CIs) were measured using unconditional logistic regression models. RESULTS: Higher dietary zinc intake was inversely associated with the risk of CRC in the total population [adjusted OR (aOR) = 0.80, 95% CI 0.66-0.96, p for trend = 0.018]. In the codominant model, G+ carriers of the SLC30A8 rs3802177 with higher consumption of zinc were observed to have a significantly lower risk of CRC in all participants (p for interaction = 0.020). In females, GG carriers with higher zinc intake showed a stronger protective effect against the development of CRC (p for interaction = 0.008). CONCLUSIONS: In summary, our findings suggest an inverse association between dietary zinc intake and CRC risk, and this relationship may be modified by SLC30A8 rs3802177 polymorphism.

Preoperative magnetic resonance imaging of anal fistulas with scrotal extension: a retrospective study.

Introduction: This study aimed to elucidate the magnetic resonance (MR) characteristics of anal fistulas extending to the scrotum, and the applicable rules, and to correlate MR features with surgical findings. Methods: We conducted a retrospective study in 150 consecutive patients with anal fistulas extending into the scrotum, who were diagnosed and underwent surgery at University Medical Center Ho Chi Minh City between January 2017 and April 2022. MR findings were evaluated and compared with surgical findings using Cohens kappa coefficient (k) with a 95% confidence interval. Results: 150 patients (mean age 37.6 ± 10.9 years) with 166 fistulas, including 150 anal fistulas with scrotal extension. Most fistulas were low transsphincteric (80.0%, 120/150 patients). There was a strong agreement for primary tract classification and detecting the location of internal openings between MRI and surgical findings with k = 0.83 (0.780.87) and k = 0.89 (0.85 0.93) (p<0.001), respectively. There is a significant correlation between the location of internal openings and the type of fistula (p<0.05). Low transsphincteric fistulas were predominant in the anterior group (103/122 patients vs. 10/19 patients), while in the posterior group, it was more common in the high transsphincteric fistulas (7/19 patients vs. 14/122 patients), and the intersphincteric fistulas (1/19 patients vs. 5/122 patients); and the suprasphincteric fistulas were only seen in the posterior group (1 patient). Conclusion: Anal fistulas with scrotal extension are exceptions to Goodsalls rule. Albeit long-tract fistulas, most are low transsphincteric and have anterior internal openings.

Upregulation of immunoproteasome PSMB8 is associated with Parkinson's disease.

BACKGROUND: Immunoproteasome, a part of ubiquitin-proteasome system, is involved in immune response as well as protein degradation. However, the relationship between immunoproteasome and Parkinson's disease (PD) was not evaluated clearly. We hypothesized that the shift of immunoproteasome attributes to PD pathogenesis due to its role in inflammation and protein homeostasis. OBJECTIVE: To determine whether immunoproteasome in peripheral blood mononuclear cells (PBMC) and brain is expressed differently between patients with PD and healthy controls (HC). METHODS: Blood samples were collected from 19 HC to 40 patients with PD of comparable ages. Peripheral blood mononuclear cells were isolated and followed by RT-qPCR to measure the mRNA levels of three catalytic subunits of immunoproteasome, namely, PSMB8, PSMB9, and PSMB10. Then, the protein levels of each subunit were measured by western blot. Finally, we confirmed the altered immunoproteasome subunit in the post-mortem human brain of PD. RESULTS: In PBMCs, PSMB8 mRNA expression of PD group significantly increased compared to HC (p = 0.004), whereas PSMB9 and PSMB10 mRNA were not different between the PD and HC. The ratio of PSMB10 and PSMB8 mRNA (PSMB10/8 ratio) also reflected the significant difference between the PD and HC (p = 0.002). The PSMB10/8 ratio was well correlated with the UPDRS total and Part III score in the early stage of PD (Hoehn and Yahr ≤2.5) or drug-naïve PD subgroups. In terms of the protein level of immunoproteasome subunits in PBMCs, the increase of PSMB8 protein was observed in PD compared to HC (p = 0.0009), while PSMB9 and PSMB10 were not different between groups. Finally, we confirmed that immunoproteasome PSMB8 was expressed abundantly in the postmortem PD brain compared with normal control. CONCLUSION: Our novel findings implicate that immunoproteasome PSMB8 is engaged in PD pathomechanism.

Genome-wide association study reveals useful QTL and genes controlling the fatty acid composition in rice bran oil using Vietnamese rice landraces.

In rice (Oryza sativa L.), rice bran contains valuable nutritional constituents, such as high unsaturated fat content, tocotrienols, inositol, γ-oryzanol, and phytosterols, all of which are of nutritional and pharmaceuticals interest. There is now a rising market demand for rice bran oil, which makes research into their content and fatty acid profile an area of interest. As it is evident that lipid content has a substantial impact on the eating, cooking, and storage quality of rice, an understanding of the genetic mechanisms that determine oil content in rice is of great importance, equal to that of rice quality. Therefore, in this study, we performed a genome-wide association study on the composition and oil concentration of 161 Vietnamese rice varieties. Five categories of fatty acids in rice bran were discovered and the bran oil concentration profile in different rice accessions was identified. We also identified 229 important markers related to the fatty acid composition of bran oil, distributed mainly on chromosomes 1 and 7. Seven quantitative trait loci and five potential genes related to unsaturated fatty acid content were detected, including OsKASI, OsFAD, OsARF, OsGAPDH, and OsMADS29. These results provide insights into the genetic basis of rice bran oil composition, which is pivotal to the metabolic engineering of rice plants with desirable bran oil content through candidate genes selection.

Association between dietary habits and incident thyroid cancer: A prospective cohort study.

Background: In addition to the thyroid cancer (TC) risk from lifestyle and environmental factors such as radiation exposure, some studies have indicated that diet may affect TC development; however, previous findings are inconsistent. The objective of our study was to investigate the association between dietary habits and TC risk in a Korean population. Materials and methods: A total of 13,973 participants were selected after excluding ineligible subjects from the Cancer Screenee Cohort at National Cancer Center in Korea from October 2007 to December 2021. Participants were followed until May 2022 to identify incident TC cases. Information on dietary habits and general characteristics was collected using a self-report questionnaire administered at enrollment without keeping track of changes in eating habits during the follow-up period. A Cox proportional hazards model was used to determine the hazard ratio (HR) and 95% confidence interval (CI) of TC risk for each dietary factor. Results: A total of 138 incident TC cases were identified during the median follow-up period of 7.6 years. Of the 12 dietary habits evaluated, only two habits showed significant associations with TC. A significantly decreased TC risk was found among participants who consumed milk and/or dairy products 5 or more days a week [adjusted HR (aHR), 0.58; 95% CI, 0.39-0.85]. Notably, a stronger protective effect of dairy consumption was observed in participants aged ≥ 50 years (aHR, 0.44; 95% CI, 0.26-0.75), in women (aHR, 0.53; 95% CI, 0.35-0.81), and in non-smokers (aHR, 0.60; 95% CI, 0.39-0.92). There was a reduced risk of TC in participants with meal durations longer than 10 min (aHR, 0.58; 95% CI, 0.41-0.83). However, this association was limited to individuals aged ≥ 50 years (aHR, 0.49; 95% CI, 0.31-0.79), women (aHR, 0.61; 95% CI, 0.41-0.90), and non-smokers (aHR, 0.62; 95% CI, 0.41-0.92). Conclusion: Our findings suggest that consuming milk and/or dairy products 5 or more days a week and having a meal duration longer than 10 min could be protective factors against TC, especially in individuals aged ≥ 50 years, women and non-smokers. Further prospective studies are needed to investigate the association of dietary intake with specific types of TC.

Next-generation sequencing-based HLA typing reveals the association of HLA-B*46:01:01 and HLA-DRB1*09:01:02 alleles with carbamazepine-induced hypersensitivity reactions in Vietnamese patients with epilepsy.

Several studies have reported an association between certain human leukocyte antigen (HLA) alleles and carbamazepine (CBZ)-induced hypersensitivity reactions in patients with epilepsy. Here, the relationship between the clinical spectrum and the HLA allele profiles in patients with CBZ-induced hypersensitivity reactions was investigated using next-generation sequence (NGS) data obtained from 65 Vietnamese patients with epilepsy, including 33 with CBZ-tolerance and 32 patients with CBZ-hypersensitivity, in which only 8 with severe cutaneous adverse drug reactions and 24 were mild-hypersensitive patients. Three loci of HLA class I (HLA-A, -B, and -C) and two loci of HLA class II (HLA-DQA1 and -DRB1) were included in our analysis. We observed a higher prevalence of three alleles, HLA-B*46:01:01, HLA-DQA1*03:02:01, and HLA-DRB1*09:01:02, in the CBZ hypersensitivity group compared to that in the CBZ tolerant group. Notably, all hypersensitive patients with HLA-DQA1*03:02:01 also harbored HLA-DRB1*09:01:02. We also used molecular modeling to gain mechanistic insight into the interactions of HLA-B*46:01 and HLA-DRB1*09:01 with CBZ. Our findings proposed the direct interaction of CBZ with peptide-binding pockets of these HLA proteins. The sensitivity and specificity of HLA-B*46:01:01 in considering with the appearance of HLA-DRB1*09:01:02 were 46.88% and 84.85%, respectively. Our data suggest that the presence of HLA-B*46:01:01/HLA-DRB1*09:01:02 is a potential marker of CBZ-induced hypersensitivity reactions in Vietnamese patients.

Mental health, functional impairment, and barriers to mental health access among cancer patients in Vietnam.

OBJECTIVE: This study evaluated the prevalence and severity of depression and anxiety symptomatology, barriers to mental health access, and correlates of functional impairment among cancer inpatients. METHODS: This cross-sectional study recruited adult cancer patients (N = 300) in June and July 2022 at the largest oncological hospital in Vietnam. Multivariable linear regression analyses examined the association between demographics, clinical characteristics, and patients' functional impairment. RESULTS: Approximately 46.3% and 27.0% showed some depression and anxiety symptomatology, while 8.0% and 3.0% experienced major depressive and anxiety symptoms, respectively. Patients reported the most impairment in mobility and capacity for life activities. More functional impairment was identified in patients with gastrointestinal cancers, those receiving radiation therapy alone, and those scoring higher on depression and anxiety than in those with cancers originating in the head, neck, or lung or those receiving chemotherapy alone. Reports of better overall health status were negatively associated with functional impairment. Patients reported extensive perceived barriers to seeking psychiatric care, including not knowing where to get mental health support (86.7%), wanting to manage mental health independently (73.7%), and thinking mental health will resolve on its own (73.7%), and denying mental health concerns (61.0%). CONCLUSION: High frequency and severity of depression and anxiety symptomatology underscore the importance of integrating mental health services into existing oncological treatment protocols. Increasing mental health literacy and provision of psychoeducation is critical to addressing barriers to mental health service access. Integration of functional impairment evaluations into hospital admission and discharge planning is also needed.

LMP1-EBV Gene Deletion Mutations and HLA Genotypes of Nasopharyngeal Cancer Patients in Vietnam.

Nasopharyngeal carcinoma (NPC) is the most common cancer among head and neck cancers in Vietnam. We aimed to identify the rate of a 30 bp deletion mutation of the LMP1-EBV gene in nasopharyngeal biopsy tissue samples, the HLA genotypes of NPC patients, and the relationship between these two targets. Patients with NPC at Can Tho Oncology Hospital from September 2014 to December 2018 were selected. A length of 30 bp of the del-LMP1-EBV gene was analyzed using a PCR technique, and the HLA genotypes in patients' blood samples were analyzed with PCR-SSO technology. HLA-B*15 gene carriers had the highest risk of 30 bp LMP1-EBV gene deletion mutation, which was found in 51 out of 70 patients (72.9%). Carriers of the HLA-B*15 allele had a 4.6-fold increased risk of a 30 bp del-LMP1-EBV gene compared with non-carriers of this allele. The initial identification of NPC was related to the 30 bp del-LMP1-EBV gene and high frequencies of the -A*02, -B*15, -DRB1*12, -DQB1*03, and -DQA1*01 HLA alleles. Our study results suggest an association of the 30 bp del-LMP1-EBV gene and the HLA-B*15 allele with NPC susceptibility.

Impact of pharmacist-initiated educational interventions on improving medication reconciliation practice in geriatric inpatients during hospital admission in Vietnam.

WHAT IS KNOWN AND OBJECTIVE: Unintentional medication discrepancies (UMDs) are common in geriatric patients during care transitions, resulting in frequent undesirable consequences. Medication reconciliation could be a useful practice to prevent or ameliorate UMD. However, this practice in Vietnamese hospitals has not been well established or standardized. This study aims to determine the effect of pharmacist-initiated educational interventions on improving medication reconciliation practice. METHODS: This prospective 6-month pre-and post-study was conducted in two internal medicine wards in a Vietnamese 800-bed public hospital. Pharmacists provided training and short-term support to physicians on medication reconciliation. Primary outcome measures were the proportions of patients with at least one UMD at admission. Secondary outcome measures were the proportions of patients with preventable adverse drug events (pADEs) score ≥0.1 due to these UMDs. Odds ratio and 95% confidence intervals were assessed based on a multivariate logistic regression model. RESULTS AND DISCUSSION: One hundred fifty-two patients were recruited in the pre-intervention phase, and 146 in the post-intervention phase. Following the intervention, the proportion of geriatric patients with ≥1 UMD at admission significantly decreased from 55.3 to 25.3 % (ORadj 0.255, 95% CI: 0.151-0.431). Similarly, the proportion of patients with a pADE ≥0.1 at admission reduced from 44.1 to 11.6% [ORadj 0.188, 95% CI: 0.105-0.340] post-intervention. WHAT IS NEW AND CONCLUSION: Our pharmacist-initiated educational interventions have demonstrated the ability to produce substantial improvement in medication reconciliation practice, reducing UMDs and potential harm. Our approach may provide an alternate option to implement medication reconciliation for jurisdictions with limited healthcare resources.

Role of NLRP3 Inflammasome in Parkinson's Disease and Therapeutic Considerations.

Parkinson's disease (PD) is the second most common neurodegenerative disease, with two main pathological features: misfolded α-synuclein protein accumulation and neurodegeneration. Inflammation has recently been identified as a contributor to a cascade of events that may aggravate PD pathology. Inflammasomes, a group of intracellular protein complexes, play an important role in innate immune responses to various diseases, including infection. In PD research, accumulating evidence suggests that α-synuclein aggregations may activate inflammasomes, particularly the nucleotide-binding oligomerization domain-leucine-rich repeat-pyrin domain-containing 3 (NLRP3) type, which exacerbates inflammation in the central nervous system by secreting proinflammatory cytokines like interleukin (IL)-18 and IL-1ß. Afterward, activated NLRP3 triggers local microglia and astrocytes to release additional IL-1ß. In turn, the activated inflammatory process may contribute to additional α-synuclein aggregation and cell loss. This review summarizes current research evidence on how the NLRP3 inflammasome contributes to PD pathogenesis, as well as potential therapeutic strategies targeting the NLRP3 inflammasome in PD.

Proteomic Profiling of Small Extracellular Vesicles Isolated from the Plasma of Vietnamese Patients with Non-Small Cell Lung Cancer Reveals Some Potential Biomarkers.

BACKGROUND: Considering the poor prognosis of non-small cell lung cancer (NSCLC), the objective of this study was to examine the potential of plasma-derived vesicles as a source of lung cancer-specific proteins. Extracellular vesicle (EV) cargos are specific to the source cells, hence they have the potential of being a source of cancer-specific proteins.  Methods: The proteins differently expressed in cancer were determined and derived from EVs isolated from the plasma of NSCLC patients at the National Lung Hospital. To this end, purification was done using gel filtration chromatography and ultracentrifugation. In addition, nano liquid chromatography mass spectrometry (LC-MS/MS) was used for analyzing. RESULTS: Fifty-seven EV-derived proteins related to NSCLC were highlighted in this research. Some of them have not been addressed before, such as EEF1A1 (elongation factor 1-α1), KPNB1 (Importin subunit beta 1), SRC (proto-oncogene tyrosine-protein kinase) and ACTC1 (actin, alpha cardiac muscle 1). This list was further confirmed through a comparison with ExoCarta and Vesiclepedia. CONCLUSION: This study is the first work to show the involvement of several novel proteins of small EV (EEF1A1, KPNB1, SRC, and ACTC1) in the progression of NSCLC. The results suggested that they could serve as novel biomarkers for non-small cell lung cancer in the future.
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PTEN-Induced Putative Kinase 1 Dysfunction Accelerates Synucleinopathy.

BACKGROUND: Mutations in PTEN-induced putative kinase 1 (PINK1) cause autosomal recessive Parkinson's disease (PD) and contribute to the risk of sporadic PD. However, the relationship between PD-related PINK1 mutations and alpha-synuclein (α-syn) aggregation-a main pathological component of PD-remains unexplored. OBJECTIVE: To investigate whether α-syn pathology is exacerbated in the absence of PINK1 after α-syn preformed fibril (PFF) injection in a PD mouse model and its effects on neurodegeneration. METHODS: In this study, 10-week-old Pink1 knockout (KO) and wildtype (WT) mice received stereotaxic unilateral striatal injection of recombinant mouse α-syn PFF. Then, α-syn pathology progression, inflammatory responses, and neurodegeneration were analyzed via immunohistochemistry, western blot analysis, and behavioral testing. RESULTS: After PFF injection, the total α-syn levels significantly increased, and pathological α-syn was markedly aggregated in Pink1 KO mice compared with Pink1 WT mice. Then, earlier and more severe neuronal loss and motor deficits occurred. Moreover, compared with WT mice, Pink1 KO mice had evident microglial/astrocytic immunoreactivity and prolonged astrocytic activation, and a higher rate of protein phosphatase 2A phosphorylation, which might explain the greater α-syn aggravation and neuronal death. CONCLUSION: The loss of Pink1 function accelerated α-syn aggregation, accumulation and glial activation, thereby leading to early and significant neurodegeneration and behavioral impairment in the PD mouse model. Therefore, our findings support the notion that PINK1 dysfunction increases the risk of synucleinopathy.