bluuebunny/crossref_metadata_2025 huggingface dataset:
Global trends of Vaccinia oncolytic virus therapy over the past two decades: Bibliometric and visual analysis
Authors: Bo Liu , Tianming Liu , Fengliang Fan , Wenping Liang , Jinzuo Han , Dongbo Xue , Biao Ma , Haijun Sun
Published: February 2023

Background

In recent years, the vaccinia oncolytic virus has entered the clinical trial stage of examination and shown good progress. It has many advantages, such as good safety, high oncolytic efficiency, and the regulation ability of the tumor microenvironment, and is expected to be successfully used in the clinical treatment of tumors in the future. However, no bibliometric analysis has so far been performed that generalizes horizontally across this field. Therefore, this study aims to assess the research status and trends in this field from a global perspective to help guide future research priorities.

Methods

In this study, the literature related to vaccinia oncolytic virus published in English on Web of Science from 2002 to 2022 was retrieved, and the bibliometric indicators were analyzed using the Histcite. Pro 2.0 tool, while VOSviewer was used to visualize the research trends and hotspots in this field.

Results

In total, 408 related studies were included. In the past 20 years, the number of related publications in this field has increased year by year, and breakthroughs were made in this field in 2008 and 2013. The research has grown rapidly since 2008, and will likely continue to expand in the years to come. The United States plays a leading role in this area. “MOLECULAR THERAPY-ONCOLYTICS”, “MOLECULAR THERAPY” and “JOURNAL OF TRANSLATIONAL MEDICINE” are core journals that publish high-quality literature on the latest advances in the field. Some authors with numerous high-quality publications include Bell JC and Szalay AA. At present, the research hotspot in this field focus on the clinical application of vaccinia oncolytic virus.

Conclusion

Overall, the number of vaccinia oncolytic virus-related studies is growing rapidly, in relation to which the United States is the most influential country. The clinical application of vaccinia oncolytic virus will affect the crucial development of future research.
LncRNAs has been identified as regulators of Myeloid-derived suppressor cells in lung cancer
Authors: Liu Yifan , Han Yukun , Zhang Yanhua , Lv Tongtong , Peng Xiaochun , Huang Jinbai
Published: February 2023

Lung tumours are widespread pathological conditions that attract much attention due to their high incidence of death. The immune system contributes to the progression of these diseases, especially non-small cell lung cancer, resulting in the fast evolution of immune-targeted therapy. Myeloid-derived suppressor cells (MDSCs) have been suggested to promote the progression of cancer in the lungs by suppressing the immune response through various mechanisms. Herein, we summarized the clinical studies on lung cancer related to MDSCs. However, it is noteworthy to mention the discovery of long non-coding RNAs (lncRNAs) that had different phenotypes and could regulate MDSCs in lung cancer. Therefore, by reviewing the different phenotypes of lncRNAs and their regulation on MDSCs, we summarized the lncRNAs’ impact on the progression of lung tumours. Data highlight LncRNAs as anti-cancer agents. Hence, we aim to discuss their possibilities to inhibit tumour growth and trigger the development of immunosuppressive factors such as MDSCs in lung cancer through the regulation of lncRNAs. The ultimate purpose is to propose novel and efficient therapy methods for curing patients with lung tumours.
Development and validation of cuproptosis-related genes in synovitis during osteoarthritis progress
Authors: Chang Bohan , Hu Zhehan , Chen Liang , Jin Zhuangzhuang , Yang Yue
Published: February 2023

Osteoarthritis (OA) is one of the most common refractory degenerative joint diseases worldwide. Synovitis is believed to drive joint cartilage destruction during OA pathogenesis. Cuproptosis is a novel form of copper-induced cell death. However, few studies have examined the correlations between cuproptosis-related genes (CRGs), immune infiltration, and synovitis. Therefore, we analyzed CRGs in synovitis during OA. Microarray datasets (GSE55235, GSE55457, GSE12021, GSE82107 and GSE176308) were downloaded from the Gene Expression Omnibus database. Next, we conducted differential and subtype analyses of CRGs across synovitis. Immune infiltration and correlation analyses were performed to explore the association between CRGs and immune cell abundance in synovitis. Finally, single-cell RNA-seq profiling was performed using the GSE176308 dataset to investigate the expression of CRGs in the various cell clusters. We found that the expression of five CRGs (FDX1, LIPT1, PDHA1, PDHB, and CDKN2A) was significantly increased in the OA synovium. Moreover, abundant and various types of immune cells infiltrated the synovium during OA, which was correlated with the expression of CRGs. Additionally, single-cell RNA-seq profiling revealed that the cellular composition of the synovium was complex and that their proportions varied greatly as OA progressed. The expression of CRGs differed across various cell types in the OA synovium. The current study predicted that cuproptosis may be involved in the pathogenesis of synovitis. The five screened CRGs (FDX1, LIPT1, PDHA1, PDHB, and CDKN2A) could be explored as candidate biomarkers or therapeutic targets for OA synovitis.
Decreased resistance to bacterial cold-water disease and excessive inflammatory response in ayu (Plecoglossus altivelis) reared at high water temperature
Authors: Kato Goshi , Nakajima Hayato , Suzuki Kyuma , Kanzawa Yuhei , Nakayasu Chihaya , Taguchi Kosei , Kurata Osamu , Sano Motohiko
Published: February 2023

Introduction

Temporal elevation of water temperature positively affects immune activity and disease resistance in poikilothermic teleost fish. The ayu, Plecoglossus altivelis, an important fish species for Japanese freshwater fisheries, is usually produced under higher water temperatures than the natural conditions to facilitate rapid growth. However, it has been reported that rearing fish at higher water temperatures inhibits the development of the thymus, suggesting that resistance to infectious diseases is reduced in ayu reared at higher water temperatures. Here, we show that decreased resistance to bacterial cold-water disease and excessive inflammatory responses occurred in ayu reared at 22°C compared with those reared at lower temperatures.

Methods

Ayu larvae were reared at 12°C, 15°C and 22°C for 77 days and fed 3% of their body weight. Thymus index and condition factor was calculated after the fish rearing. Then, ayu reared at the different temperatures were challenged with Flavobacterium psychrophilum and the fish were sampled for histopathology and gene expression analyses. Further, the fish were vaccinated with formalin-killed F. psychrophilum and continuously reared at the three different water temperatures. Serum antibody titer was determined by ELISA and cumulative mortality in each group was recorded after the bacterial challenge.

Results

Ayu reared at 22°C showed a significantly lower thymus index and higher condition factor than those reared at lower temperatures. Infiltrated leukocytes and many melanin pigments were frequently observed in the adipose tissues and spleens of ayu reared at 22°C, respectively, but not in those reared at 12°C. The gene expression levels of inflammatory cytokines such as IL-1β, IL-8 and TNFα in the spleen were significantly higher in the 22°C group than in the 12°C group. The cumulative survival rate after challenge with Flavobacterium psychrophilum was 51.7%, 40.0% and 13.3% in the 12°C, 15°C and 22°C groups, respectively. The relative percent survival values of vaccinated fish reared at 15°C and 22°C groups were lower than those reared at 12°C. Moreover, the specific antibody titer of the vaccinated fish was the lowest in the 22°C group and the highest in the 12°C group.

Discussion

These results suggest that rearing the fish under high water temperature causes excessive inflammatory responses similar to metabolic inflammation in human obesity, resulting in a decrease of disease resistance. In addition, thymic involution induced by higher water temperature probably leads the poor response to vaccination. The present study provides insights into the physiological and immunological changes of fish under global warming.
Role of mTOR inhibitor in the cellular and humoral immune response to a booster dose of SARS-CoV-2 mRNA-1273 vaccine in kidney transplant recipients
Authors: Pérez-Flores Isabel , Juarez Ignacio , Aiffil Meneses Arianne S. , Lopez-Gomez Ana , Romero Natividad Calvo , Rodriguez-Cubillo Beatriz , Moreno de la Higuera María Angeles , Peix-Jiménez Belen , Gonzalez-Garcia Raquel , Baos-Muñoz Elvira , Vilela Ana Arribi , Gómez Del Moral Manuel , Martínez-Naves Eduardo , Sanchez-Fructuoso Ana Isabel
Published: February 2023

Background

Immunocompromised patients have an increased risk of developing severe COVID disease, as well as a tendency to suboptimal responses to vaccines. The objective of this study was to evaluate the specific cellular and humoral adaptive immune responses of a cohort of kidney transplant recipients (KTR) after 3 doses of mRNA-1273 vaccine and to determinate the main factors involved.

Methods

Prospective observational study in 221 KTR (149 non infected), 55 healthy volunteers (HV) and 23 dialysis patients (DP). We evaluated anti-spike (by quantitative chemiluminescence immunoassay) and anti-nucleocapsid IgG (ELISA), percentage of TCD4+ and TCD8+ lymphocytes producing IFNγ against S-protein by intracellular flow cytometry after Spike-specific 15-mer peptide stimulation and serum neutralizing activity (competitive ELISA) at baseline and after vaccination.

Results

Among COVID-19 naïve KTR, 54.2% developed cellular and humoral response after the third dose (vs 100% in DP and 91.7% in HV), 18% only showed cell-mediated response, 22.2% exclusively antibody response and 5.6% none. A correlation of neutralizing activity with both the IgG titer (r=0.485, p<0.001) and the percentage of S-protein–specific IFNγ–producing CD8-T cells (r=0.198, p=0.049) was observed. Factors related to the humoral response in naïve KTR were: lymphocytes count pre-vaccination >1000/mm3 [4.68 (1.72-12.73, p=0.003], eGFR>30 mL/min [7.34(2.72-19.84), p<0.001], mTOR inhibitors [6.40 (1.37-29.86), p=0.018]. Infected KTR developed a stronger serologic response than naïve patients (96.8 vs 75.2%, p<0.001).

Conclusions

KTR presented poor cellular and humoral immune responses following vaccination with mRNA-1273. The immunosuppression degree and kidney function of these patients play an important role, but the only modifiable factor with a high impact on humoral immunogenicity after a booster dose was an immunosuppressive therapy including a mTOR inhibitor. Clinical trials are required to confirm these results.
Three different pathways of IgM-antibody-dependent hemolysis are mainly regulated by complement
Authors: Bartolmäs Thilo , Pruß Axel , Mayer Beate
Published: February 2023

Antibodies to red blood cells (RBCs) may hemolyze erythrocytes via Fc-mediated phagocytosis or complement-dependent. Complement activation on RBCs can be detected by C3d-direct antiglobulin test (DAT), which is the only test in immune hematology that directly targets complement. However, a positive DAT with anti-C3d cannot distinguish between C3b-mediated extravascular hemolysis, C5b-C9-mediated intravascular hemolysis and C5b-C8-mediated eryptosis. Furthermore, DAT is not suitable to estimate the strength of hemolysis. Autoimmune hemolytic anemia (AIHA) is a rare disease that is caused by autoantibodies to red blood cells that is divided in warm AIHA and in cold agglutinin disease (CAD). The causative antibodies in CAD and sometimes in warm AIHA are from the IgM class. Depending on strength of complement activation they can induce extravascular hemolysis, intravascular hemolysis and eryptosis. We studied the three types of hemolysis by use of sera from patients with CAD under various conditions. We found that additionally to the routinely applied C3d-DAT, indirect tests for complement activity (free hemoglobin and Annexin V-binding to phosphatidylserine-exposing RBCs) should be used to determine the portion of extravascular, intravascular and eryptotic hemolysis. Eryptotic hemolysis may have a significant share in clinical relevant CAD or IgM warm AIHA, which should be considered for successful treatment.
Aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with HIV
Authors: Grønbæk Sylvester Klöcker , Høgh Julie , Knudsen Andreas Dehlbæk , Pham Michael Huy Cuong , Sigvardsen Per Ejlstrup , Fuchs Andreas , Kühl Jørgen Tobias , Køber Lars , Gerstoft Jan , Benfield Thomas , Ostrowski Sisse Rye , Kofoed Klaus Fuglsang , Nielsen Susanne Dam
Published: February 2023

Introduction

People living with HIV (PLWH) are at twice the risk of developing cardiovascular diseases and have more than four times higher odds of aortic aneurysm (AA) than the uninfected population. However, biomarkers of AA in PLWH are yet to be discovered. We aimed to investigate whether circulating biomarkers reflecting platelet activation, hemostasis and endothelial disruption, i.e. sCD40L, D-dimer, syndecan-1, and thrombomodulin, were associated with AA in PLWH.

Methods

Five hundred seventy one PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study ≥40 years of age with an available contrast-enhanced CT scan as well as available biomarker analyses were included. The biomarkers were analyzed on thawed plasma. For each biomarker, we defined high level as a concentration in the upper quartile and low level as a concentration below the upper quartile. For D-dimer, the cut-off was defined as the lower limit of detection. Using unadjusted and adjusted logistic and linear regression models, we analyzed associations between AA and sCD40L, D-dimer, syndecan-1, and thrombomodulin, respectively in PLWH.

Results

PLWH had median (IQR) age 52 years (47-60), 88% were male, median (IQR) time since HIV diagnosis was 15 years (8-23), and 565 (99%) were currently on antiretroviral treatment. High level of sCD40L was associated with lower odds of AA in both unadjusted (odds ratio, OR, 0.23 (95% CI 0.07-0.77;P=0.017)) and adjusted models (adjusted OR, aOR, 0.23 (95% CI 0.07-0.78;P=0.019)). Detectable level of D-dimer was associated with higher odds of AA in both unadjusted (OR 2.76 (95% CI 1.34-5.67;P=0.006)) and adjusted models (aOR 2.22 (95% CI 1.02-4.85;P=0.045)).

Conclusions

SCD40L was associated with lower odds of AA whereas D-dimer was independently associated with higher odds of AA in PLWH. This calls for further investigations into specific biomarkers to aid early diagnosis of AA in PLWH.
Analysis of immunotherapeutic response-related signatures in esophageal squamous-cell carcinoma
Authors: Zheng Bohao , Li Jie , Zhang Mengdi , Zhang Pengju , Deng Weiwei , Pu Yang
Published: February 2023

Background

Esophageal squamous cell carcinoma (ESCC) is one of the most common and lethal malignant diseases. Immunotherapy has been widely studied and has exhibited potential in ESCC treatment. However, there are only a portion of ESCC patients have benefited from immunotherapy. We herein identified immunotherapeutic response-related signatures (IRRS) and evaluated their performance in ESCC prognosis and immunotherapeutic responsiveness.

Methods

We constructed an IRRS using the gene expression data of 274 ESCC patients based on y -30significantly differentially expressed genes, which were compared responders and non-responders from various patient cohorts treated with immunotherapy. Survival analysis was performed in both the GSE53625 and TCGA-ESCC cohorts. We also explored the differences in the tumor microenvironment between the high-IRRS and low-IRRS score groups using single-cell data as a reference. Three immunotherapy cohorts were used to verify the value of the IRRS in predicting immunotherapy response.

Results

Twelve immunotherapy-related genes were selected to construct a signature score and were validated as independent prognostic predictors for patients with ESCC. Patients with high IRRS scores exhibited an immunosuppressive phenotype. Therefore, patients with low IRRS scores may benefit from immunotherapy.

Conclusions

IRRS score is a biomarker for immunotherapy response and prognosis of ESCC.
Pathogenesis and treatment of Sjogren’s syndrome: Review and update
Authors: Zhan Qipeng , Zhang Jianan , Lin Yubin , Chen Wenjing , Fan Xinzou , Zhang Dunfang
Published: February 2023

Sjogren’s syndrome (SS) is a chronic autoimmune disease accompanied by multiple lesions. The main manifestations include dryness of the mouth and eyes, along with systemic complications (e.g., pulmonary disease, kidney injury, and lymphoma). In this review, we highlight that IFNs, Th17 cell-related cytokines (IL-17 and IL-23), and B cell-related cytokines (TNF and BAFF) are crucial for the pathogenesis of SS. We also summarize the advances in experimental treatment strategies, including targeting Treg/Th17, mesenchymal stem cell treatment, targeting BAFF, inhibiting JAK pathway, et al. Similar to that of SLE, RA, and MS, biotherapeutic strategies of SS consist of neutralizing antibodies and inflammation-related receptor blockers targeting proinflammatory signaling pathways. However, clinical research on SS therapy is comparatively rare. Moreover, the differences in the curative effects of immunotherapies among SS and other autoimmune diseases are not fully understood. We emphasize that targeted drugs, low-side-effect drugs, and combination therapies should be the focus of future research.
Case report: Resuscitative endovascular balloon occlusion after iatrogenic injury of the common iliac artery during neurosurgical dorsal lumbar microdiscectomy
Authors: Fiedler Mascha O. , Böckler Dittmar , Giese Henrik , Popp Erik , Schmitt Felix C. F. , Weigand Markus A. , Erhart Philipp
Published: February 2023

Introduction and importance

This case report describes resuscitative endovascular balloon occlusion (REBOA) of the aorta in a patient with life-threatening iatrogenic bleeding of the right common iliac artery during elective dorsal lumbar spine surgery. REBOA is an emergency procedure for temporary intra-aortic balloon occlusion being increasingly reported and published since its inauguration in 1954. The interdisciplinary management of hemorrhage and technical notes for a successful REBOA procedure will be presented.

Case presentation

A 53-year-old female patient was admitted to the neurosurgery clinic suffering from left-sided L5 radiculopathy. During surgery, the anterior longitudinal ligament was perforated and an arterial vessel was lacerated. The patient became hemodynamically unstable demanding prompt supine repositioning and cardiopulmonary resuscitation (CPR). REBOA enabled cardiovascular stabilization after 90 min of CPR and laparotomy with vascular reconstruction and contributed to the survival of the patient without major clinical deficits. The patient was discharged from the ICU after 7 days.

Clinical discussion

Resuscitative endovascular balloon occlusion of the aorta is an emergency procedure to control life-threatening hemorrhage. REBOA should be available on-scene and applied by well-trained vascular surgery personnel to control vascular complications or extend to emergency laparotomy and thoracotomy with aortic cross-clamping in case of in-hospital non-controllable hemorrhages. In case of ongoing CPR, we recommend surgical groin incision, open puncture of the pulseless common femoral artery, and aortic balloon inflation in REBOA zone I. Hereby, fast access and CPR optimization for heart and brain perfusion are maintained.

Conclusion

Training for REBOA is the decisive factor to control selected cases of in-house and outpatient massive arterial abdominal bleeding complications.
Analysis of lysine acetylation in tomato spot wilt virus infection in Nicotiana benthamiana
Authors: Gong Yanwei , Li Ying , Liu Dongyang , Jiang Lianqiang , Liang Hui , Wu Yuanhua , Wang Fenglong , Yang Jinguang
Published: February 2023

Introduction

Kac is a model for all acylation modification studies. Kac plays a critical role in eukaryotes and prokaryotes. It is mainly involved in six major biological functions: gene expression, signal transduction, cell development, protein conversion, metabolism, and metabolite transport.

Method

We investigated and compared the acetylation modification of proteins in healthy and tomato spot wilt virus (TSWV)-infected Nicotiana benthamiana leaves.

Result

We identified 3,418 acetylated lysine sites on 1962 proteins acetylation of proteins in the TSWV-infected and control groups were compared; it was observed that 408 sites on 294 proteins were upregulated and 284 sites on 219 proteins (involved in pentose phosphate, photosynthesis, and carbon fixation in photosynthesis) were downregulated after the infection. Overall, 35 conserved motifs were identified, of which xxxkxxxxx_K_ Rxxxxxxxxx represented 1,334 (31.63%) enrichment motifs and was the most common combination. Bioinformatic analysis revealed that most of the proteins with Kac sites were located in the chloroplast and cytoplasm. They were involved in biological processes, such as cellular and metabolic processes.

Discussion

In conclusion, our results revealed that Kac may participate in the regulation of TSWV infection in N. benthamiana.
Heavy metal bioremediation using microbially induced carbonate precipitation: Key factors and enhancement strategies
Authors: Zhang Wenchao , Zhang Hong , Xu Ruyue , Qin Haichen , Liu Hengwei , Zhao Kun
Published: February 2023

With the development of economy, heavy metal (HM) contamination has become an issue of global concern, seriously threating animal and human health. Looking for appropriate methods that decrease their bioavailability in the environment is crucial. Microbially induced carbonate precipitation (MICP) has been proposed as a promising bioremediation method to immobilize contaminating metals in a sustainable, eco-friendly, and energy saving manner. However, its performance is always affected by many factors in practical application, both intrinsic and external. This paper mainly introduced ureolytic bacteria-induced carbonate precipitation and its implements in HM bioremediation. The mechanism of HM immobilization and in-situ application strategies (that is, biostimulation and bioaugmentation) of MICP are briefly discussed. The bacterial strains, culture media, as well as HMs characteristics, pH and temperature, etc. are all critical factors that control the success of MICP in HM bioremediation. The survivability and tolerance of ureolytic bacteria under harsh conditions, especially in HM contaminated areas, have been a bottleneck for an effective application of MICP in bioremediation. The effective strategies for enhancing tolerance of bacteria to HMs and improving the MICP performance were categorized to provide an in-depth overview of various biotechnological approaches. Finally, the technical barriers and future outlook are discussed. This review may provide insights into controlling MICP treatment technique for further field applications, in order to enable better control and performance in the complex and ever-changing environmental systems.
The relationship between serum klotho and cognitive performance in a nationally representative sample of US adults
Authors: Linghui Deng , Simin Yu , Zilong Zhang , Yuxiao Li , Shi Qiu , Birong Dong
Published: February 2023

Purpose

Aging is the primary risk factor for cognitive decline. Serum klotho, as an anti-aging protein, may be involved in cognitive decline. Thus, we aim to explorer the correlation between serum klotho and cognitive performance among an older adult population in the United States.

Methods

We performed a cross-sectional study using data from NHANES 2011–2014. Serum klotho was analyzed by ELISA. Cognitive function was measured by Establish a Registry for Alzheimer’s Disease (CERAD) test, Animal Fluency test and Digit Symbol Substitution Test (DSST) score. The relationship between serum klotho and cognition was analyzed by a multivariable regression model.

Results

A total of 2,171 participants aged 60–79 years were included. Median serum klotho concentration was 851.52 pg./ml (SD = 294.07). We also categorized serum klotho concentrates into quartiles. After fully adjusting pertinent variables, compared to those with lowest klotho levels (206.3–658.4 pg./ml), individuals with highest klotho concentrates (983.3–3,456 pg./ml) had a higher CERAD score [β (95%CI): 0.97 (0.25, 1.69) p = 0.008] and DSST score [β (95%CI): 1.86 (0.25, 3.47), p = 0.024].

Conclusion

Our findings indicated that, among the general population of American older adults, serum klotho concentrates may serve as a marker of cognitive health. The benefits of klotho on aging process and neurodegenerative disorders should be paid more attention.
Examining the intersection of cognitive and physical function measures: Results from the brain networks and mobility (B-NET) study
Authors: Thompson Atalie C. , Miller Michael E. , Handing Elizabeth P. , Chen Haiying , Hugenschmidt Christina E. , Laurienti Paul J. , Kritchevsky Stephen B.
Published: February 2023

Background and objectives

Although evidence exists that measures of mobility and cognition are correlated, it is not known to what extent they overlap, especially across various domains. This study aimed to investigate the intersection of 18 different objective cognitive and physical function measures from a sample of unimpaired adults aged 70 years and older.

Research design and methods

Canonical correlation analysis was utilized to explore the joint cross-sectional relationship between 13 cognitive and 6 physical function measures in the baseline visit of the Brain Networks and Mobility Function (B-NET) Study (n = 192).

Results

Mean age of participants was 76.4 years. Two synthetic functions were identified. Function 1 explained 26.3% of the shared variability between the cognition and physical function variables, whereas Function 2 explained 19.5%. Function 1 termed “cognitive and physical speed” related the expanded Short Physical Performance Battery (eSPPB), 400-m walk speed, and Dual Task gait speed measures of physical function to semantic fluency animals scores, Digit Symbol Coding (DSC), and Trail Making Test B. Function 2 termed “complex motor tasks and cognitive tasks” related the Force Plate Postural Sway Foam Task and Dual Task to the following cognitive variables: MoCA Adjusted Score, Verbal Fluency L words, Craft story immediate and delayed recall, and Trail Making Test B.

Discussion and implications

We identified groups of cognitive and physical functional abilities that were linked in cross-sectional analyses, which may suggest shared underlying neural network pathway(s) related to speed (Function 1) or complexity (Function 2).

Translational significance

Whether such neural processes decline before measurable functional losses or may be important targets for future interventions that aim to prevent disability also remains to be determined.
Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies
Authors: Ghatak Swagata , Nakamura Tomohiro , Lipton Stuart A.
Published: February 2023

Alzheimer’s disease (AD) is arguably the most common cause of dementia in the elderly and is marked by progressive synaptic degeneration, which in turn leads to cognitive decline. Studies in patients and in various AD models have shown that one of the early signatures of AD is neuronal hyperactivity. This excessive electrical activity contributes to dysregulated neural network function and synaptic damage. Mechanistically, evidence suggests that hyperexcitability accelerates production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that contribute to neural network impairment and synapse loss. This review focuses on the pathways and molecular changes that cause hyperexcitability and how RNS-dependent posttranslational modifications, represented predominantly by protein S-nitrosylation, mediate, at least in part, the deleterious effects of hyperexcitability on single neurons and the neural network, resulting in synaptic loss in AD.
A novel MYORG mutation causes primary familial brain calcification with migraine: Case report and literature review
Authors: Song Tingwei , Zhao Yuwen , Wen Guo , Du Juan , Xu Qian
Published: February 2023

Primary familial brain calcification (PFBC) is a disorder in which pathologic calcification of the basal ganglia, cerebellum, or other brain regions with bilateral symmetry occurs. Common clinical symptoms include dysarthria, cerebellar symptoms, motor deficits, and cognitive impairment. Genetic factors are an important cause of the disease; however autosomal recessive (AR) inheritance is rare. In 2018, the myogenesis-regulated glycosidase (MYORG) gene was the first to be associated with AR-PFBC. The present case is a 24-year-old woman with AR-PFBC that presented with migraine at the age of 16 years. Symmetrical patchy calcifications were seen in the bilateral cerebellopontine nuclei, thalamus, basal ganglia, and radiocoronal area on computed tomography and magnetic resonance imaging. AR-PFBC with migraine as the main clinical symptom is rare. Whole-exome sequencing revealed a compound heterozygous mutation in the MYORG gene, one of which has not been previously reported. Our case highlights the pathogenic profile of the MYORG gene, and demonstrates the need for exclusion of calcium deposits in the brain for migraine patients with AR inheritance.
Sleep apnea in people with Down syndrome: Causes and effects of physical activity?
Authors: Nguyen Duy-Thai , Bricout Véronique-Aurélie , Tran Hong-Tram , Pham Van-Hung , Duong-Quy Sy
Published: February 2023

Poor sleep quality is recognized as a major risk factor for poor health, increasing the incidence of serious chronic diseases. In people with Down syndrome, sleep apnea prevalence is significantly greater, it is caused by genetic, anatomical, endocrine, and metabolic abnormalities. The consequences of sleep disruption due to sleep apnea are very serious, especially in terms of neurocognitive and cardiovascular effects, leading to reduced life expectancy and quality of life in this population. However, the management, care, and treatment of related disorders in people with Down syndrome are still inadequate and limited. Therefore, this article wants to increase understanding and awareness about sleep apnea and the benefits of physical activity in improving sleep quality in the Down syndrome community, families, and their care specialists.
A bibliometric analysis on traumatic brain injury in forensic medicine of a half-century (1972–2021)
Authors: Wang Yufang , Chen Qianqian , Dang Xingxing , Lu Wanqing , Zhang Xinran , Yan He , Niu Shuliang , Yan Xisheng , Yan Jie
Published: February 2023

Traumatic brain injury (TBI) is among the most common injuries in forensic medicine, the identification of which is of particular importance in forensic practice. To reveal the circumstances and trends of TBI in the forensic field, we used the Web of Science (WoS) database for comprehensive retrieval. We made a metrological analysis of 1,089 papers in the past 50 years (1972–2021). The United States and Germany have the most forensic research on TBI. Diffuse axonal injury (DAI) has been the focus of attention for many years, and much effort has been devoted to its diagnosis in forensic pathology. Infants and children are the subgroups of most concern, especially in infant and child abuse cases. Research on identifying shaken baby syndrome has received increasing attention in recent years. Overall, our study provides a comprehensive list and analysis of the articles regarding TBI in legal medicine, which may shed light on recognizing the trends and research hotspots in this field.
Hypothermia impairs glymphatic drainage in traumatic brain injury as assessed by dynamic contrast-enhanced MRI with intrathecal contrast
Authors: Gu Wenquan , Bai Yingnan , Cai Jianguo , Mi Honglan , Bao Yinghui , Zhao Xinxin , Lu Chen , Zhang Fengchen , Li Yue-hua , Lu Qing
Published: February 2023

Introduction

The impact of hypothermia on the impaired drainage function of the glymphatic system in traumatic brain injury (TBI) is not understood.

Methods

Male Sprague–Dawley rats undergoing controlled cortical impact injury (CCI) were subjected to hypothermia or normothermia treatment. The rats undergoing sham surgery without CCI were used as the control. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with intrathecal administration of low- and high-molecular-weight contrast agents (Gd-DTPA and hyaluronic acid conjugated Gd-DTPA) was performed after TBI and head temperature management. The semiquantitative kinetic parameters characterizing the contrast infusion and cleanout in the brain, including influx rate, efflux rate, and clearance duration, were calculated from the average time-intensity curves.

Results and discussion

The qualitative and semiquantitative results of DCE-MRI obtained from all examined perivascular spaces and most brain tissue regions showed a significantly increased influx rate and efflux rate and decreased clearance duration among all TBI animals, demonstrating a significant impairment of glymphatic drainage function. This glymphatic drainage dysfunction was exacerbated when additional hypothermia was applied. The early glymphatic drainage reduction induced by TBI and aggravated by hypothermia was linearly related to the late increased deposition of p-tau and beta-amyloid revealed by histopathologic and biochemical analysis and cognitive impairment assessed by the Barnes maze and novel object recognition test. The glymphatic system dysfunction induced by hypothermia may be an indirect alternative pathophysiological factor indicating injury to the brain after TBI. Longitudinal studies and targeted glymphatic dysfunction management are recommended to explore the potential effect of hypothermia in TBI.
Chemical composition of the Kaempferia galanga L. essential oil and its in vitro and in vivo antioxidant activities
Authors: Wang Si-Yu , Cai Lei , Yang Na , Xu Fang-Fang , Wu Yun-Shan , Liu Bo
Published: February 2023

Introduction

Oxidative stress is closely related to the development of many diseases. Essential oils (EOs) show potent antioxidant activity from natural sources.Kaempferia galanga L. is an important medicine rich in high-value essential oil (KGEO). However, the antioxidant activity of KGEO remains to be fully studied.

Methods

Chemical composition of KGEO was analyzed using gas chromatography-mass spectrometry (GC-MS). The antioxidant activity was determined using the DPPH, ABTS, hydroxyl radical scavenging assays and reducing power assayin vitro. A zebrafish model was used to evaluate the protective effect of KGEO against H2O2-induced oxidative stress damagein vivo.

Results

The major components of KGEO were found to betransethyl p-methoxycinnamate (32.01%), n-pentadecane (29.14%) andtransethyl cinnamate (19.50%).In vitropharmacological results showed that KGEO had good free radical scavenging capacity in DPPH, ABTS, and hydroxyl radical scavenging assays (IC50values: 19.77 ± 1.28, 1.41 ± 0.01, and 3.09 ± 0.34 mg/mL, respectively) and weak reducing capacity in the reducing power assay (EC50value: 389.38 ± 4.07 mg/mL).In vivozebrafish experiments results indicated that the survival rate and heart rate increased, and ROS generation, cell death, and lipid peroxidation were attenuated after KGEO treatment. In addition, a decrease in malondialdehyde (MDA) levels and increases in superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were observed in the KGEO-treated groups.

Discussion

This study validated thein vitroandin vivoantioxidant activities of KGEO, which provides a theoretical basis for a profound study of KGEO and its application in the pharmaceutical, food and cosmetic industries.
Associations of adherence to Mediterranean-like diet pattern with incident rosacea: A prospective cohort study of government employees in China
Authors: Chen Peng , Yang Ziye , Fan Zhihua , Wang Ben , Tang Yan , Xiao Yi , Chen Xiang , Luo Dan , Xiao Shuiyuan , Li Ji , Xie Hongfu , Shen Minxue
Published: February 2023

Background

Despite of growing evidence on gastrointestinal comorbidities of rosacea, there was a lack of literatures regarding the role of diet on rosacea.

Objectives

To investigate the relationship between adherence to a Mediterranean-like diet pattern and the risk of incident rosacea.

Methods

This was a prospective cohort study of government employees aged >20 years conducted between January 2018 and December 2021 from five cities of Hunan province of China. At baseline, participants completed a food frequency questionnaire and participated in a skin examination. Presence of rosacea was determined by certified dermatologists. Subsequent skin examinations during follow-up were performed every one-year interval since the entry of the study. The Mediterranean diet score (MDS) was generated based on seven food groups (whole grains, red meats, fish, raw vegetables, legumes, fruits and nuts). Binary logistic regression models adjusted for potential confounders were used to estimate risks for incident rosacea.

Results

Of the 3,773 participants who completed at least two consecutive skin examinations, 3,496 were eligible for primary analyses. With a total follow-up of 8,668 person-years, we identified 83 incident rosacea cases. After full adjustments for covariates, the MDS was associated a decreased risk of incident rosacea (aOR: 0.84, 95% CI: 0.72, 0.99; Ptrend = 0.037 for 1-point increment of MDS). In subgroup analyses by body mass index (BMI), this inverse association was consistently observed in the lowest and medium tertiles of BMI (<24.5 kg/m2), but not in the highest tertile of BMI (≥24.5 kg/m2), with a significant interaction effect (P < 0.001).

Conclusions

Our results suggested that adherence to a Mediterranean-like diet pattern might reduce the risk of incident rosacea among non-overweight individuals.
Relationship between NUDT21 mediated alternative polyadenylation process and tumor
Authors: Xiao Shan , Gu Huan , Deng Li , Yang Xiongtao , Qiao Dan , Zhang Xudong , Zhang Tian , Yu Tao
Published: February 2023

Alternative polyadenylation (APA) is a molecular process that generates diversity at the 3’ end of RNA polymerase II transcripts from over 60% of human genes. APA and microRNA regulation are both mechanisms of post-transcriptional regulation of gene expression. As a key molecular mechanism, Alternative polyadenylation often results in mRNA isoforms with the same coding sequence but different lengths of 3’ UTRs, while microRNAs regulate gene expression by binding to specific mRNA 3’ UTRs. Nudix Hydrolase 21 (NUDT21) is a crucial mediator involved in alternative polyadenylation (APA). Different studies have reported a dual role of NUDT21 in cancer (both oncogenic and tumor suppressor). The present review focuses on the functions of APA, miRNA and their interaction and roles in development of different types of tumors.NUDT21 mediated 3’ UTR-APA changes can be used to generate specific signatures that can be used as potential biomarkers in development and disease. Due to the emerging role of NUDT21 as a regulator of the aforementioned RNA processing events, modulation of NUDT21 levels may be a novel viable therapeutic approach.
Chemo-immunotherapy for metastatic non-squamous NSCLC in a patient with HIV infection: A case report
Authors: Inno Alessandro , Lattuada Emanuela , Foti Giovanni , Gori Stefania
Published: February 2023

Activity and safety data of chemo-immunotherapy for patients with metastatic NSCLC and known HIV infection are still limited, since HIV-positive patients were generally excluded from clinical trials. Here we report the case of a metastatic NSCLC patient with HIV infection and undetectable viral load treated with first-line chemo-immunotherapy (pembrolizumab, carboplatin and pemetrexed), achieving a meaningful and durable objective response, with no treatment-related adverse events and no HIV-related complications. This report suggests that NSCLC patients with virologically controlled HIV infection can be safely treated with chemo-immunotherapy and should not be excluded from this treatment based on their viral infection only.
Multiple ectopic recurrent germ cell tumors after total pineal mature teratoma removal: A case report and literature review
Authors: Han Lei , Song Ye , Fang Luxiong , Qi Songtao
Published: February 2023

Intracranial germ cell tumors (GCTs) are highly heterogeneous and rare, and the recurrence of mature teratomas is uncommon. There is limited data on the systematic management of multiple recurrent tumors following total teratoma removal. Herein, we report repeated relapsing GCTs with different histological subtypes and locations after en bloc total resection of a pineal mature teratoma. A 14-year-old patient underwent total resection of a tumor in the pineal region and histopathology revealed a mature cystic teratoma. Four years later, the patient experienced a recurrence of the suprasellar tumor, which occurred several times over the next eight years. The tumor was successfully eliminated after multiple surgeries, radiotherapy and chemotherapy. By the time the paper was submitted, the patient had not had a recurrence of the tumor and was in the good physical condition and leading a normal life. Based on this case, we discussed the pathogenesis of recurrent mature teratoma and the therapeutic strategy of multiple recurrent GCTs.
Modified anterior approach preserving Retzius space versus standard anterior approach robot-assisted radical prostatectomy: A matched-pair analysis
Authors: Li Hui , Yang Chao , Liao Zhonghong , Wang Kaihong , Zhang Yida , Cao Runfu
Published: February 2023

Objective

To compare our initial perioperative and postoperative outcomes of the modified anterior approach (MA) with Retzius space preservation robot-assisted radical prostatectomy (RARP) with the standard anterior approach (SA) RARP.

Materials and methods

A retrospective analysis was performed on 116 patients with RARP completed by the same surgeon between September 2019 and March 2022. They were divided into SA-RARP group (77 cases) and MA-RARP group (39 cases). Propensity score matching was performed using eight preoperative variables, including age, BMI, preoperative PSA, biopsy Gleason score, prostate volume, D’Amico risk classification, SHIM, and clinical T stage. Functional outcome was assessed by urine pad count and SHIM after surgery, and oncological outcome was assessed by statistics of postoperative pathological findings as well as follow-up postoperative PSA. The median follow-up was 13 months and 17 months for MA-RARP and SA-RARP groups respectively.

Results

Propensity score matching was performed 1:1, and baseline data were comparable between the two groups after matching. Comparison of postoperative data: MA-RARP group had less mean EBL than SA-RARP group (200 vs 150 ml, p = 0.033). PSM did not differ between groups (p = 1). In terms of urinary control recovery, the MA-RARP group showed significant advantages in urinary control recovery at 24 h, 2 weeks, 1 month and 3 months after catheter removal, respectively (48.6% vs 5.7%, p < 0.001; 80% vs 22.9%, p < 0.001; 94.3% vs 51.4%, p < 0.001; 100% vs 74.3%, p = 0.002). This advantage gradually disappeared 6 months or more after surgery. The median time to recovery of sexual function was shorter in the MA-RARP group (165 vs 255 d, p = 0.001).

Conclusion

MA-RARP is safe and reliable, and can achieve better early urinary control function and sexual function recovery while achieving the primary tumor control goal.
Case Report: Disease progression of renal cell carcinoma containing a novel putative pathogenic KAT6A::NRG1 fusion on Ipilimumab- Nivolumab immunotherapy. A case study and review of the literature
Authors: Dawood Almas , MacMahon Suzanne , Dang My-Anh Tran , Tran Maxine G. B. , Bex Axel , Boleti Ekaterini , Sheikh Soha El
Published: February 2023

Renal cell carcinoma still carries a poor prognosis despite therapeutic advancements. Detection of genetic mutations is vital in improving our understanding of this disease as well as potential role in targeted therapy. Here we present a case of a 49 year old man with an aggressive renal cell carcinoma bearing a novel pathogenic KAT6A::NRG1 fusion. We will explore the clinical presentation, histological and molecular diagnostics, treatment and disease progression. We will discuss the relevance of this unique fusion and comparisons with cancer cases with similar genetic mutations. Further research is warranted for such cases, in order to facilitate better targeted treatments.
Improving anti-tumor efficacy of low-dose Vincristine in rhabdomyosarcoma via the combination therapy with FOXM1 inhibitor RCM1
Authors: Donovan Johnny , Deng Zicheng , Bian Fenghua , Shukla Samriddhi , Gomez-Arroyo Jose , Shi Donglu , Kalinichenko Vladimir V. , Kalin Tanya V.
Published: February 2023

Rhabdomyosarcoma (RMS) is a highly metastatic soft-tissue sarcoma that often develops resistance to current therapies, including vincristine. Since the existing treatments have not significantly improved survival, there is a critical need for new therapeutic approaches for RMS patients. FOXM1, a known oncogene, is highly expressed in RMS, and is associated with the worst prognosis in RMS patients. In the present study, we found that the combination treatment with specific FOXM1 inhibitor RCM1 and low doses of vincristine is more effective in increasing apoptosis and decreasing RMS cell proliferation in vitro compared to single drugs alone. Since RCM1 is highly hydrophobic, we developed innovative nanoparticle delivery system containing poly-beta-amino-esters and folic acid (NPFA), which efficiently delivers RCM1 to mouse RMS tumors in vivo. The combination of low doses of vincristine together with intravenous administration of NPFA nanoparticles containing RCM1 effectively reduced RMS tumor volumes, increased tumor cell death and decreased tumor cell proliferation in RMS tumors compared to RCM1 or vincristine alone. The combination therapy was non-toxic as demonstrated by liver metabolic panels using peripheral blood serum. Using RNA-seq of dissected RMS tumors, we identified Chac1 as a uniquely downregulated gene after the combination treatment. Knockdown of Chac1 in RMS cells in vitro recapitulated the effects of the combination therapy. Altogether, combination treatment with low doses of vincristine and nanoparticle delivery of FOXM1 inhibitor RCM1 in a pre-clinical model of RMS has superior anti-tumor effects and decreases CHAC1 while reducing vincristine toxicity.