bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights into epigenetic regulation of cyp19a via comparative analysis using the scombrid chub mackerel as model
Authors: Galotta Mariel , Dam Anh Tuan , Eto Yuhei , Toyoda Atsushi , Itoh Takehiko , Mohapatra Sipra , Ogino Yukiko , Saitou Marie , Matsuyama Michiya , Chakraborty Tapas , Ohta Kohei
Published: June 2024

Sexual development and reproduction are largely linked to epigenetic changes in many fish species. However, understanding of epigenetic regulation in scombrid species, such as tunas and mackerels, is limited. This study investigates DNA methylation’s impact on cyp19a expression, crucial for estrogen synthesis, focusing on chub mackerel. Given the commercial significance of scombrids and susceptibility of marine fish to environmental changes, elucidating epigenetic mechanisms, particularly in the context of global warming, becomes imperative. We aimed to generalize observations from chub mackerel to other scombrids. Additionally, we studied DNA methylation patterns across fish with different sexual systems to understand aromatase regulation’s phenotypic plasticity. Our in silico analysis revealed highly conserved promoter sequences within scombrids, sharing TFBS like Foxl2, FOS::JUN, ESRR, and Sox3, while CpG content varies. This indicates a conserved regulatory network controlling gene expression. We found sexual dimorphism in DNA methylation, with males hypermethylated and aromatase expression downregulated. Despite similar dnmt1 expression, tet1, tet2, and tet3 were higher expressed in females, suggesting that the observed DNA methylation patterns are maintained through active demethylation rather than differential methylation. Gonochoristic Japanese anchovy and protogynous bamboo leaf wrasse displayed similar trends, but species-specific methylation patterns highlight DNA methylation’s complex role in gonadal changes. In vitro assays confirmed methylation’s regulatory role and identified an SF-1 binding site relevant for promoter activation in chub mackerel. Another studied SF-1 site, present in both chub mackerel and bamboo leaf wrasse, showed regulatory effects, indicating potential similar regulatory mechanisms for cyp19a expression. Overall, our findings suggest that while global methylation affects cyp19a transcription, the variation in CpG density and location could be introducing nuances in its epigenetic regulation. This study contributes to our understanding of the cyp19a regulation in fish gonad maturation.
Research on the resistance of cement-based materials to sulfate attack based on MICP technology
Authors: Zhang Yong , Peng Geng , Li Ai , Yang Xinrui , Kong Shuaidi , An Yutong , Tian Junhao , Sun Xupeng
Published: June 2024

To evaluate the effect of Microbial Induced Calcium Carbonate Precipitation (MICP) on the enhancement of early resistance to sulfate attack of cementitious materials. In this paper, firstly, the effect of Bacillus subtilis (BM) on the carbonation depth as well as the carbonation rate of standard as well as carbonation-conditioned cementitious sand specimens was investigated. Secondly, the compressive strength and volumetric deformation of the specimens at different ages of immersion in sulfate solution were investigated. Finally, the changes of hydration products before and after the addition of BM were analyzed by X-ray diffraction analysis (XRD), and the microscopic pore structure of the specimens after erosion was analyzed by low-field nuclear magnetic resonance (LF-NMR) and scanning electron microscope (SEM), which revealed the mechanism of the improvement of BM on the resistance to sulfate erosion of the cementitious materials. The results showed that the initial compressive strength of BM carbonised curing specimens, ordinary carbonised curing specimens and BM standard curing specimens were increased by 42.0%, 34.0% and 4.0%, respectively, compared with the ordinary standard curing specimens, respectively, compared with the control group, and the loss of the final compressive strength was reduced by 37.4%, 25.4%, and 14.5%, and the expansion rate was reduced by 31.3%, 22.0%, after sulfate erosion for 6 months, 5.2%, and porosity decreased by 24.2%, 13.6%, and 9.9%. Microbial mineralization accelerated the reaction between Ca2+ in the pore solution and atmospheric CO2, and the calcite formed filled the pores to make the structure denser, increasing the initial compressive strength of the specimens and reducing the loss of properties when exposed to sulfate solution. Therefore, the application of MICP technology in cementitious materials provides a new direction for the development of durable and sustainable cementitious materials.
Molecular detection of rifampicin-resistant Mycobacterium tuberculosis by polymerase chain reaction in Ethiopia: a systematic review and meta-analysis
Authors: Birhanu Molla Yigzaw , Bekele Getamesay Molla , Jemberie Selamawit Shita
Published: June 2024

Introduction

Tuberculosis is a contagious bacterial disease caused by Mycobacterium tuberculosis. The emergence and spread of drug-resistant strains of M. tuberculosis in both developing and developed countries has made diagnosis, treatment, and control of tuberculosis more difficult. The PCR assay, which is a fast and sensitive technique and an alternative method for detecting multidrug-resistant tuberculosis, is used to determine rifampicin (RIF) resistance. There is no single figure in Ethiopia that represents rifampicin-resistant tuberculosis and that is why this study was conducted to overcome the inconsistency of the results of the previous studies.

Methods

Studies were researched from five major electronic databases. Studies which were cross-sectional in design, published, and written in English were included. The data were extracted using Microsoft Excel, and the data were managed and analyzed using Stata™ Version 17.0 statistical software. The Forest plot was used to check the presence of heterogeneity. The publication bias, meta-regression, and subgroup analysis were used to find out the source of heterogeneity. A random effect analysis model was used to pool the prevalence of RR TB from primary studies, and associated factors of RR among TB patients were identified using Meta regression. The presence of association was reported using OR with 95% CI.

Results

The overall pooled prevalence of tuberculosis was 14.9% (95% CI: 13.34, 16.46), of these approximately 7.48% (95% CI: 6.30, 8.66) showed rifampicin-resistant tuberculosis in Ethiopia. Among the computed variables, 2.05% living with HIV1.39 (95%CI: 1.13, 1.72) and having a history of TB treatment (95%CI: 1.34, 3.15) were identified as significant factors associated with RR TB in Ethiopia.

Conclusion

Drug-resistant TB is one of the prevalent emerging infectious diseases among TB patients, which affects approximately one out of every thirteen TB patients. Having TB-HIV coinfection and a history of prior TB treatment were identified as significant factors associated with RR TB. To prevent and control RR TB, patients should complete their follow-up course; the health professionals should educate the actions taken by the patients when they experience drug toxicity and side effects; and the Minister of Health should initiate telemedicine and recruit tracers to overcome TB patients’ default and have good drug adherence and retention after initiation of the treatment.
Effectiveness of acupuncture on urinary retention after radical hysterectomy for cervical cancer in China: a systematic review and meta-analysis
Authors: Guo Yong , Pan Haixia , Chen Siyang , Tian Minne , Huang Yanmei , Zhou Ying
Published: June 2024

Background

Cervical cancer is one of the most common malignant tumors worldwide. Radical hysterectomy is the first choice for patients with early-stage cervical cancer. Studies have suggested that acupuncture may be a more effective therapy for the prevention and treatment of urinary retention after radical hysterectomy.

Objective

To systematically evaluate the clinical efficacy of acupuncture in the prevention and treatment of urinary retention after radical hysterectomy.

Methods

We searched the Cochrane library, Web of science, PubMed, Embase, Chinese Biomedical Literature Database, Wanfang database, Wipu database, China National Knowledge Infrastructure Database and ClinicalTrials.gov with the time from inception until December 2023, to collect randomized controlled studies on the clinical efficacy of acupuncture for prevention and treatment of urinary retention after radical hysterectomy. Literature meeting criteria was screened for data extraction. Quality evaluation was performed according to the Cochrane Handbook for Systematic Reviews of Interventions. And meta-analysis was performed using RevMan5.3 and stata14.0 software.

Results

22 Randomized controlled trials with 1,563 patients, 854 in treatment group and 709 in control group, were included totally. Meta-analysis results showed that: the total effective rate in acupuncture group was higher than that in control group, with a statistically significant difference [relative risk (RR)] = 1.43, 95% confidence interval (CI 1.22, 1.68), p < 0.0001; the rate of urinary tract infection in acupuncture group was lower than that in control group, with a statistically significant difference [RR] = 0.23, 95% CI (0.07, 0.78), p < 0.05; the time of indwelling urinary catheter was reduced in acupuncture group compared with control group, with a statistically significant mean difference = −3.45, 95% CI (−4.30, −2.59), p < 0.00001; the incidence of urinary retention was lower in acupuncture group than in control group, and the difference was statistically significant [RR = 0.37, 95% CI (0.27, 0.50), p < 0.00001]; the residual urine volume was reduced in acupuncture group compared with control group, with a statistically significant mean difference = −50.73, 95% CI (−63.61, −7.85), p < 0.00001.

Conclusion

Acupuncture treatment based on conventional therapy can better prevent and improve urinary retention after radical hysterectomy for cervical cancer, could be a better option for them.

Systematic review registration

Registered by PROSPERO and the registration number is CRD42023452387.
Advancements of non-invasive prenatal testing: the role of obstetricians
Authors: Eltabbakh Nada , Mohasin Yalnaz , Jeddy Rafiea
Published: June 2024

Since its debut in 2011, Non-Invasive Prenatal Testing (NIPT) has continually demonstrated its effectiveness in detecting an expanding number of diseases. NIPT offers a less invasive approach to prenatal chromosomal disease screening, providing prospective parents with vital information to better prepare for their potential pregnancy outcomes. NIPT was primarily designed for screening trisomy 13, 18, and 21. However, its scope has since broadened to encompass microdeletions and autosomal dominant monogenic diseases. Conversely, the normalization of NIPT can have unintended consequences. Some patients opt for NIPT without any medical indications, driven by a desire to remain cautious. This over-screening for chromosomal abnormalities can exacerbate pregnancy-related anxiety, as individuals might feel pressured into taking the test unnecessarily. While NIPT can be highly successful when conducted correctly, it is not infallible, and obstetricians play a crucial role in managing patient expectations. This includes providing genetic counseling to individuals with relevant genetic information regarding their personal and family histories. In the context of NIPT, a bioinformatics analysis is performed on a cell-free DNA (cfDNA) sample extracted from the mother’s placenta to determine the fetal fraction (FF). This FF measurement is vital for quality control and ensuring statistical confidence in the test results. Raising awareness among clinicians about the significance of FF enhances patient care and alleviate concerns about the possibility of failed NIPT. This paper aims to explore the ongoing debates and more specifically the significance and pitfalls of NIPT on a psychosocial and ethical scale, all while highlighting the importance of genetic counseling.
Direct prediction of antimicrobial resistance in Pseudomonas aeruginosa by metagenomic next-generation sequencing
Authors: Cao Lichao , Yang Huilin , Huang Zhigang , Lu Chang , Chen Fang , Zhang Jiahao , Ye Peng , Yan Jinjin , Zhang Hezi
Published: June 2024

Objective

Pseudomonas aeruginosa has strong drug resistance and can tolerate a variety of antibiotics, which is a major problem in the management of antibiotic-resistant infections. Direct prediction of multi-drug resistance (MDR) resistance phenotypes of P. aeruginosa isolates and clinical samples by genotype is helpful for timely antibiotic treatment.

Methods

In the study, whole genome sequencing (WGS) data of 494 P. aeruginosa isolates were used to screen key anti-microbial resistance (AMR)-associated genes related to imipenem (IPM), meropenem (MEM), piperacillin/tazobactam (TZP), and levofloxacin (LVFX) resistance in P. aeruginosa by comparing genes with copy number differences between resistance and sensitive strains. Subsequently, for the direct prediction of the resistance of P. aeruginosa to four antibiotics by the AMR-associated features screened, we collected 74 P. aeruginosa positive sputum samples to sequence by metagenomics next-generation sequencing (mNGS), of which 1 sample with low quality was eliminated. Then, we constructed the resistance prediction model.

Results

We identified 93, 88, 80, 140 AMR-associated features for IPM, MEM, TZP, and LVFX resistance in P. aeruginosa. The relative abundance of AMR-associated genes was obtained by matching mNGS and WGS data. The top 20 features with importance degree for IPM, MEM, TZP, and LVFX resistance were used to model, respectively. Then, we used the random forest algorithm to construct resistance prediction models of P. aeruginosa, in which the areas under the curves of the IPM, MEM, TZP, and LVFX resistance prediction models were all greater than 0.8, suggesting these resistance prediction models had good performance.

Conclusion

In summary, mNGS can predict the resistance of P. aeruginosa by directly detecting AMR-associated genes, which provides a reference for rapid clinical detection of drug resistance of pathogenic bacteria.
Novel therapeutic regimens against Helicobacter pylori: an updated systematic review
Authors: Huang Ting-Ting , Cao Yong-Xiao , Cao Lei
Published: June 2024

Helicobacter pylori (H. pylori) is a strict microaerophilic bacterial species that exists in the stomach, and H. pylori infection is one of the most common chronic bacterial infections affecting humans. Eradicating H. pylori is the preferred method for the long-term prevention of complications such as chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. However, first-line treatment with triple therapy and quadruple therapy has been unable to cope with increasing antibacterial resistance. To provide an updated review of H. pylori infections and antibacterial resistance, as well as related treatment options, we searched PubMed for articles published until March 2024. The key search terms were “H. pylori”, “H. pylori infection”, “H. pylori diseases”, “H. pylori eradication”, and “H. pylori antibacterial resistance.” Despite the use of antimicrobial agents, the annual decline in the eradication rate of H. pylori continues. Emerging eradication therapies, such as the development of the new strong acid blocker vonoprazan, probiotic adjuvant therapy, and H. pylori vaccine therapy, are exciting. However, the effectiveness of these treatments needs to be further evaluated. It is worth mentioning that the idea of altering the oxygen environment in gastric juice for H. pylori to not be able to survive is a hot topic that should be considered in new eradication plans. Various strategies for eradicating H. pylori, including antibacterials, vaccines, probiotics, and biomaterials, are continuously evolving. A novel approach involving the alteration of the oxygen concentration within the growth environment of H. pylori has emerged as a promising eradication strategy.
Changes in brain structure and function during early aging in patients with chronic low back pain
Authors: Zu Yao , Zhang Zhou , Hao Zengming , Jiang Zimu , Chen Ke , Wang Yu , Zou Changcheng , Ge Le , Yu Qiuhua , Zheng Fuming , Wang Chuhuai
Published: June 2024

Objective

To explore the structural and functional changes in cognition-related brain regions in patients with chronic low back pain (CLBP) at earlier ages, and explore the impact of the interaction between CLBP and age on the brain.

Methods

Seventy-six patients with CLBP were recruited and divided into “younger” age group (20–29 years, YA), “middle” age group (30–39 years, MA), and “older” age group (40–49 years, OA). All patients underwent functional magnetic resonance imaging (fMRI) as well as clinical psychological and pain-related symptoms assessments.

Results

Structural analysis showed that patients in OA group had lower gray matter (GM) volumes in the orbitofrontal cortex (OFC) bilaterally and the right superior frontal gyrus (SFG) compared to YA group. The resting-state brain activity analysis showed that amplitude of low-frequency fluctuation (ALFF) values in the bilateral postcentral gyrus and left ventral medial prefrontal cortex (mPFC) were significantly different in the OA group. The functional connectivity (FC) in the right ventral dorsolateral prefrontal cortex (DLPFC) and the right insula was significantly decreased in the OA group compared to the YA and MA groups. Likewise, the FC in the left caudal parahippocampal gyrus (PHG) and left inferior parietal lobule (IPL) were significantly lower in the MA and OA groups compared to the YA group. In addition, both the structural properties and the FC values of these brain regions were significantly correlated with age.

Conclusion

This preliminary study concludes that CLBP affects the aging process. The synergistic effects of CLBP and aging accelerate the functional and structural decline of certain areas of the brain, which not only affects pain processing, but are also may be associated with cognitive declines.
Safety and effectiveness of thermal radiofrequency applied to the musculocutaneous nerve for patients with spasticity
Authors: Otero-Villaverde Sergio , Formigo-Couceiro Jacobo , Martin-Mourelle Rosa , Montoto-Marques Antonio
Published: June 2024

Objective

Evaluate safety and effectiveness of thermal radiofrequency in the musculocutaneous nerve in patients with focal elbow flexor spasticity.

Design

Ambispective observational follow-up study. Patients with focal spasticity secondary to central nervous system injury with elbow flexor pattern who received thermal radiofrequency treatment in the musculocutaneous nerve between 2021 and 2023 were included.

Subjects

12 patients.

Methods

Ultrasound-guided thermal radiofrequency was applied to the musculocutaneous nerve at 80°C for 90 s. Effectiveness was assessed prior to thermal radiofrequency and at 6 months using scales to measure pain (VAS), spasticity (MAS), disability (DAS), quality of life (SQol-6D), patient-perceived and physician-perceived satisfaction (PIG-C, PGA), and goal attainment (GAS). Elbow joint range of motion was evaluated via goniometry. Safety was evaluated by assessing side effects.

Results

Patients had statistically significant improvements in spasticity (p = 0.003), severe elbow flexion (p = 0.02), pain (p = 0.046), functioning (p < 0.05), and spasticity-related quality of life (p < 0.05 in three sections). Furthermore, treatment goals were attained. Patient- and physician-perceived clinical improvement was achieved. Regarding side effects, two patients had dysesthesia that was self-limiting, with maximum duration of 1 month.

Conclusion

Thermal radiofrequency in the musculocutaneous nerve can be a safe, effective treatment for patients with severe spasticity with an elbow flexor pattern.
Sex differences in Huntington's disease from a neuroinflammation perspective
Authors: Risby-Jones Grace , Lee John D. , Woodruff Trent M. , Fung Jenny N.
Published: June 2024

Huntington's disease (HD) is a debilitating neurodegenerative condition characterized by motor, cognitive and psychiatric abnormalities. Immune dysregulation, prominently featuring increased immune activity, plays a significant role in HD pathogenesis. In addition to the central nervous system (CNS), systemic innate immune activation and inflammation are observed in HD patients, exacerbating the effects of the Huntingtin (HTT) gene mutation. Recent attention to sex differences in HD symptom severity underscores the need to consider gender as a biological variable in neurodegenerative disease research. Understanding sex-specific immune responses holds promise for elucidating HD pathophysiology and informing targeted treatment strategies to mitigate cognitive and functional decline. This perspective will highlight the importance of investigating gender influence in HD, particularly focusing on sex-specific immune responses predisposing individuals to disease.
No effect of whole-hand water flow stimulation on skill acquisition and retention during sensorimotor adaptation
Authors: Le Cong Dat , Sato Daisuke , Ikarashi Koyuki , Ochi Genta , Fujimoto Tomomi , Yamashiro Koya
Published: June 2024

Introduction

Repetitive somatosensory stimulation (RSS) is a conventional approach to modulate the neural states of both the primary somatosensory cortex (S1) and the primary motor cortex (M1). However, the impact of RSS on skill acquisition and retention in sensorimotor adaptation remains debated. This study aimed to investigate whether whole-hand water flow (WF), a unique RSS-induced M1 disinhibition, influences sensorimotor adaptation by examining the hypothesis that whole-hand WF leads to M1 disinhibition; thereby, enhancing motor memory retention.

Methods

Sixty-eight young healthy participants were randomly allocated to three groups based on the preconditioning received before motor learning: control, whole-hand water immersion (WI), and whole-hand WF. The experimental protocol for all the participants spanned two consecutive days. On the initial day (day 1), baseline transcranial magnetic stimulation (TMS) assessments (T0) were executed before any preconditioning. Subsequently, each group underwent their respective 30 min preconditioning protocol. To ascertain the influence of each preconditioning on the excitability of the M1, subsequent TMS assessments were conducted (T1). Following this, all participants engaged in the motor learning (ML) of a visuomotor tracking task, wherein they were instructed to align a cursor with a target trajectory by modulating the pinch force. Upon completion of the ML session, final TMS assessments (T2) were conducted. All participants were required to perform the same motor learning 24 h later on day 2.

Results

The results revealed that whole-hand WF did not significantly influence skill acquisition during sensorimotor adaptation, although it did reduce intracortical inhibition. This phenomenon is consistent with the idea that S1, rather than M1, is involved in skill acquisition during the early stages of sensorimotor adaptation. Moreover, memory retention 24 h after skill acquisition did not differ significantly across the three groups, challenging our initial hypothesis that whole-hand WF enhances memory retention throughout sensorimotor adaptation. This could be due to the inability of whole-hand WF to alter sensorimotor connectivity and integration, as well as the nature of the plastic response elicited by the preconditioning.

Discussion

In conclusion, these findings suggest that although whole-hand WF attenuates intracortical inhibition, it does not modulate skill acquisition or motor memory retention during sensorimotor adaptation.
Advancements in brain-machine interfaces for application in the metaverse
Authors: Liu Yang , Liu Ruibin , Ge Jinnian , Wang Yue
Published: June 2024

In recent years, with the shift of focus in metaverse research toward content exchange and social interaction, breaking through the current bottleneck of audio-visual media interaction has become an urgent issue. The use of brain-machine interfaces for sensory simulation is one of the proposed solutions. Currently, brain-machine interfaces have demonstrated irreplaceable potential as physiological signal acquisition tools in various fields within the metaverse. This study explores three application scenarios: generative art in the metaverse, serious gaming for healthcare in metaverse medicine, and brain-machine interface applications for facial expression synthesis in the virtual society of the metaverse. It investigates existing commercial products and patents (such as MindWave Mobile, GVS, and Galea), draws analogies with the development processes of network security and neurosecurity, bioethics and neuroethics, and discusses the challenges and potential issues that may arise when brain-machine interfaces mature and are widely applied. Furthermore, it looks ahead to the diverse possibilities of deep and varied applications of brain-machine interfaces in the metaverse in the future.
A clathrin mediated endocytosis scaffolding protein, Intersectin 1, changes in an isoform, brain region, and sex specific manner in Alzheimer’s disease
Authors: Jaye Sierra , Sandau Ursula S. , McFarland Trevor J. , Woltjer Randy L. , Saugstad Julie A.
Published: June 2024

Alzheimer’s disease (AD) is the most common form of dementia and is characterized by the accumulation of amyloid-beta (Aβ) plaques and neurofibrillary Tau tangles in the brain. We previously identified a set of candidate AD microRNAs (miRNAs) in human cerebrospinal fluid (CSF) and used a target prediction pipeline to identify mRNAs and pathways that could potentially be regulated by the miRNAs. Of these pathways, clathrin mediated endocytosis (CME) was selected for further investigation. CME is altered in multiple brain cell types in AD and is implicated in early cellular phenotypes such as enlarged early endosomes and pathogenic processing of Aβ. However, a comprehensive evaluation of major CME hub proteins in humans with AD across multiple brain regions is lacking. Thus, we used immunoblots to evaluate human post-mortem AD and control (CTL) frontal cortex (FC; AD n = 22, CTL n = 23) and hippocampus (HP; AD n = 34, CTL n = 22) for changes in Intersectin 1 (ITSN1), Phosphatidylinositol Binding Clathrin Assembly Protein gene (PICALM), Clathrin Light Chain (CLT), FCH and Mu Domain Containing Endocytic Adaptor 1 (FCHO1), Adaptor Related Protein Complex 2 (AP2) Subunit Alpha 1 (AP2A1), and Dynamin 2 (DNM2). Of these, we found that in AD, ITSN1-long (ITSN1-L) was decreased in the FC of males and HP of females, while ITSN1-short was increased in the HP of both males and females. We further evaluated ITSN1-L levels in cortex (CTX) and HP of the 5xFAD mouse model of Aβ pathology at different timepoints during aging and disease progression by immunoblot (n = 5–8 per group). At 3 months, female 5xFAD exhibited an increase of ITSN1-L in CTX but a decrease at 6 and 9 months. Additionally, immunofluorescent staining of 5xFAD primary HP neurons showed an increase of ITSN1-L in matured 5xFAD neurons at 21 and 28 days in vitro. Together, our studies show that in AD, isoforms of ITSN1 change in a brain region-and sex-dependent manner. Further, changes in ITSN1-L are transient with levels increasing during early Aβ accumulation and decreasing during later progression. These findings suggest that ITSN1 expression, and consequently CME activity, may change depending on the stage of disease progression.
A critical review of Ginger’s (Zingiber officinale) antioxidant, anti-inflammatory, and immunomodulatory activities
Authors: Ayustaningwarno Fitriyono , Anjani Gemala , Ayu Azzahra Mutiara , Fogliano Vincenzo
Published: June 2024

Ginger (Zingiber officinale) is a rhizome that has been used as a healthy herbal plant for years. Ginger’s chemical components are recognized to provide beneficial health effects, namely as antioxidants and anti-inflammatory agents with the potential to operate as immunomodulators. This literature review covers numerous publications concerning ginger’s immunomodulatory potential, associated with antioxidant and anti-inflammatory effects in modifying the body’s immune system. Pathophysiology of oxidative stress and inflammation were introduced before diving deep down into the herbal plants as an immunomodulator. Ginger’s antioxidant and anti-inflammatory properties are provided by gingerol, shogaols, paradol, and zingerone. Ginger’s antioxidant mechanism is linked to Nrf2 signaling pathway activation. Its anti-inflammatory mechanism is linked to Akt inhibition and NF-KB activation, triggering the release of anti-inflammatory cytokines while reducing proinflammatory cytokines. Ginger consumption as food and drink was also explored. Overall, ginger and its active components have been shown to have strong antioxidant properties and the potential to reduce inflammation. Challenges and future prospects of ginger are also elaborated for future development. Future collaborations between researchers from various fields, including chemists, biologists, clinicians, pharmacists, and the food industry, are required further to investigate the effect of ginger on human immunity. Collaboration between researchers and industry can help accelerate the advancement of ginger applications.
Discovery and application of food catalysts to promote the coupling of PQQ (quinone) with amines
Authors: Ikemoto Kazuto , Imaruoka Satoko , Ishak Nur Syafiqah Mohamad
Published: June 2024

Background

Biocatalysts (enzymes) play a crucial role in catalyzing specific reactions across various industries, often offering environmentally friendly and sustainable alternatives to chemical catalysts. However, their catalytic activities are susceptible to denaturation. In this study, we present the discovery of novel protein-based biocatalysts derived from processed foods, including skimmed milk, soy milk, cheese, and dried tofu. These food catalysts exhibit high availability, low cost, safety, and thermo-stability.

Results

Focusing on the physiologically intriguing coenzyme pyrroloquinoline quinone (PQQ), we observed that the reaction with glycine to form imidazolopyrroquinoline (IPQ) did not proceed efficiently when PQQ was present at very low concentrations. Surprisingly, in the presence of protein-based foods, this reaction was significantly accelerated. Notably, skimmed milk enhanced the PQQ detection limit (600 times lower) during high-performance liquid chromatography (HPLC) following IPQ derivatization. Milk appears to facilitate the reaction between PQQ and various amino acids, primary amines, and secondary amines. Further investigations revealed that food catalysis operates through a non-enzymatic mechanism. Additionally, nuclear magnetic resonance spectroscopy demonstrated that milk components interacted with amino substrates due to the ability of amines to react with quinones on colloidal surfaces.

Conclusion

These practical food catalysts not only contribute to environmental safety but also hold significance across diverse scientific domains. Non-enzymatic protein catalysts find applications in biocatalysis, organic synthesis, food technology, analytical chemistry, and fundamental nutritional and evolutionary studies.
Research progress on pharmacological properties and application of probiotics in the fermentation of Scutellaria baicalensis Georgi
Authors: Guo Fangyu , Li Chunhai , Dou Jiaxin , Liang Jie , Chen Zouquan , Xu Zhenshang , Wang Ting
Published: June 2024

Scutellaria baicalensis Georgi is a medicinal herb with a rich history of use in traditional Chinese medicine. This review concentrates on the chemical constituents of Scutellaria baicalensis Georgi, with a particular emphasis on flavonoids such as baicalin, baicalein, and wogonin. Additionally, it examines the effects of probiotic fermentation on the plant’s chemical profile and pharmacological actions. Evidence suggests that probiotic fermentation markedly modifies the bioactive components of Scutellaria baicalensis Georgi, thereby augmenting its medicinal potency. The paper delves into the mechanisms by which the primary active constituents of Scutellaria baicalensis Georgi are altered during fermentation and how these changes influence its pharmacological properties. This review aims to lay a theoretical groundwork for the clinical utilization of Scutellaria baicalensis Georgi and the formulation of innovative therapeutic approaches.
Benefit of a multimodal approach combining chemotherapy and surgery in oligometastatic gastric cancer: experience from a tertiary referral center
Authors: Maratta Maria Grazia , Vitale Antonio , Basso Michele , Vivolo Raffaella , Di Monte Elena , Biondi Alberto , Di Giorgio Andrea , Rosa Fausto , Tondolo Vincenzo , Agnes Annamaria , Tortora Giampaolo , Strippoli Antonia , Pozzo Carmelo
Published: June 2024

Introduction

Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide with limited therapeutic options. The aim of this study was to analyze the value of adding surgery to the first-line treatment in patients with oligometastatic GC (OGC).

Methods

This retrospective study included patients with OGC who underwent induction chemotherapy followed by surgery of both primary tumor and synchronous metastasis between April 2012 and April 2022. Endpoints were overall survival (OS) and relapse-free survival (RFS) analyzed by the Kaplan–Meier method. Prognostic factors were assessed with the Cox model.

Results

Data from 39 patients were collected. All cases were referred to our multidisciplinary tumor board (MTB) to evaluate the feasibility of radical surgery. After a median follow-up of 33.6 months (mo.), median OS was 26.6 mo. (95% CI 23.8–29.4) and median RFS was 10.6 mo. (95% CI 6.3–14.8). Pathologic response according to the Mandard criteria (TRG 1–3, not reached versus 20.5 mo. for TRG 4–5; HR 0.23, p=0.019), PS ECOG ≤ 1 (26.7 mo. for PS ≤ 1 versus 11.2 mo. for PS >1; HR 0.3, p=0.022) and a low metastatic burden (26.7 mo. for single site versus 12.9 mo. for ≥2 sites; HR 0.34, p=0.039) were related to good prognosis. No major intraoperative complications nor surgery-related deaths occurred in our series.

Discussion

A sequential strategy of preoperative chemotherapy and radical surgical excision of both primary tumor and metastases was demonstrated to significantly improve OS and RFS. Multidisciplinary evaluation is mandatory to identify patients who could benefit from this strategy.
Predicting nodal metastasis progression of oral tongue cancer using a hidden Markov model in MRI
Authors: Gang Qiangqiang , Feng Jie , Kauczor Hans-Ulrich , Zhang Ke
Published: June 2024

Objectives

The presence of occult nodal metastases in patients with oral tongue squamous cell carcinomas (OTSCCs) has implications for treatment. More than 30% of patients will have occult nodal metastases, yet a considerable number of patients undergo unnecessary invasive neck dissection to confirm nodal status. In this work, we propose a probabilistic model for lymphatic metastatic spread that can quantify the risk of microscopic involvement at the lymph node level (LNL) given the location of macroscopic metastases and the tumor stage using the MRI method.

Materials and methods

A total of 108 patients of OTSCCs were included in the study. A hidden Markov model (HMM) was used to compute the probabilities of transitions between states over time based on MRI. Learning of the transition probabilities was performed via Markov chain Monte Carlo sampling and was based on a dataset of OTSCC patients for whom involvement of individual LNLs was reported.

Results

Our model found that the most common involvement was that of level I and level II, corresponding to a high probability of 𝑝b1 = 0.39 ± 0.05, 𝑝b2 = 0.53 ± 0.09; lymph node level I had metastasis, and the probability of metastasis in lymph node II was high (93.79%); lymph node level II had metastasis, and the probability of metastasis in lymph node III was small (7.88%). Lymph nodes progress faster in the early stage and slower in the late stage.

Conclusion

An HMM can produce an algorithm that is able to predict nodal metastasis evolution in patients with OTSCCs by analyzing the macroscopic metastases observed in the upstream levels, and tumor category.
The prognostic and predictive value of homologous recombination deficiency status in patients with advanced stage epithelial ovarian carcinoma after first-line platinum-based chemotherapy
Authors: Xu Yiqing , Chen Yi-Ju Amy , Wu Yunhong , Saverimuthu Angela , Jadhav Archana , Bhuiyan Rehana , Sandler Jason , Yio Jiang , Kumar Vivek
Published: June 2024

Objective

Homologous recombination (HR) comprises series of interrelated pathways that repair double-stranded DNA breaks and inter-strand crosslinks. It provides support for DNA replication to recover stalled or broken replication forks. Compared with homologous recombination proficiency (HRP), cancers with homologous recombination deficiency (HRD) are more likely to undergo cell death when treated with DNA-damaging agents, such as platinum agents, and have better disease control.

Methods

Patients diagnosed with stage III/IV ovarian cancer, early stages with recurrence, who received adjuvant chemotherapy after debulking surgery, and who also had known HR status were eligible.

Results

Forty-four patients were included, with 21 in the HRD group (including 8 with germline mutations) and 23 in the HRP group. The HRD group was composed predominantly of serous carcinoma (95.2%), while mucinous (n=3) and clear cell (n=1) cases were all found in the HRP group. Stage III/IV disease was 66.7% and 91.3% in HRD and HRP groups, respectively (p=0.064). Patients who were optimally debulked to no residual disease was 90.0% and 72.7% (p=0.243), respectively. Late line use of PARP inhibitors was 33.3% and 17.4% (p=0.303). Median PFS was 22.5 months (95% CI, 18.5 - 66.6) and 21.5 months (95% CI, 18.3-39.5) (p=0.49) in HRD and HRP respectively. Median platinum free interval (PFI) was 15.8 months (95% CI 12.4-60.4) and 15.9 months (95% CI 8.3-34.1) (p=0.24), respectively. Median OS was 88.2 months (95% CI 71.2-NA) and 49.7 months (95% CI 35.1-NA) (p=0.21). The PFS of the patients with germline BRCA mutations (n=5) was 54.3 months (95% CI 23.1-NA) and 21.5 months (95% CI 18.3-39.5) in the HRP group (p=0.095); the PFI difference was 47.7 months (95% CI 17.6-NA) in the BRCA mutation group, and 15.9 months (95% CI 12.4-60.4) in HRP, showing statistical significance (p=0.039); while the median OS was NA and 49.7 months (95% CI 35.1-NA) respectively (p=0.051). When adding two additional patients with somatic BRCA mutations to the germline BRCA mutation carriers, the median OS is NA (95% CI 73, NA) versus 49.7 months (95% CI 35.1, NA) for HRP (p=0.045).

Conclusions

HRD status was not associated with longer PFS or PFI in advanced ovarian cancer who received first line adjuvant platinum-based chemotherapy. Its role as a prognostic marker for overall survival is suggested, particularly in the subgroup with germline and somatic BRCA mutations.
Development of prognostic signatures and risk index related to lipid metabolism in ccRCC
Authors: Chen Wenbo , Zhao Zhenyu , Zhou Hao , Dong Shuang , Li Xiaoyu , Hu Sheng , Zhong Shan , Chen Ke
Published: June 2024

Background

Clear cell renal cell carcinoma (ccRCC) is a metabolic disorder characterized by abnormal lipid accumulation in the cytoplasm. Lipid metabolism-related genes may have important clinical significance for prognosis prediction and individualized treatment.

Methods

We collected bulk and single-cell transcriptomic data of ccRCC and normal samples to identify key lipid metabolism-related prognostic signatures. qPCR was used to confirm the expression of signatures in cancer cell lines. Based on the identified signatures, we developed a lipid metabolism risk score (LMRS) as a risk index. We explored the potential application value of prognostic signatures and LMRS in precise treatment from multiple perspectives.

Results

Through comprehensive analysis, we identified five lipid metabolism-related prognostic signatures (ACADM, ACAT1, ECHS1, HPGD, DGKZ). We developed a risk index LMRS, which was significantly associated with poor prognosis in patients. There was a significant correlation between LMRS and the infiltration levels of multiple immune cells. Patients with high LMRS may be more likely to respond to immunotherapy. The different LMRS groups were suitable for different anticancer drug treatment regimens.

Conclusion

Prognostic signatures and LMRS we developed may be applied to the risk assessment of ccRCC patients, which may have potential guiding significance in the diagnosis and precise treatment of ccRCC patients.
Progress and pitfalls of gene editing technology in CAR-T cell therapy: a state-of-the-art review
Authors: Moradi Vahid , Khodabandehloo Elnaz , Alidadi Mehdi , Omidkhoda Azadeh , Ahmadbeigi Naser
Published: June 2024

CAR-T cell therapy has shown remarkable promise in treating B-cell malignancies, which has sparked optimism about its potential to treat other types of cancer as well. Nevertheless, the Expectations of CAR-T cell therapy in solid tumors and non-B cell hematologic malignancies have not been met. Furthermore, safety concerns regarding the use of viral vectors and the current personalized production process are other bottlenecks that limit its widespread use. In recent years the use of gene editing technology in CAR-T cell therapy has opened a new way to unleash the latent potentials of CAR-T cell therapy and lessen its associated challenges. Moreover, gene editing tools have paved the way to manufacturing CAR-T cells in a fully non-viral approach as well as providing a universal, off-the-shelf product. Despite all the advantages of gene editing strategies, the off-target activity of classical gene editing tools (ZFNs, TALENs, and CRISPR/Cas9) remains a major concern. Accordingly, several efforts have been made in recent years to reduce their off-target activity and genotoxicity, leading to the introduction of advanced gene editing tools with an improved safety profile. In this review, we begin by examining advanced gene editing tools, providing an overview of how these technologies are currently being applied in clinical trials of CAR-T cell therapies. Following this, we explore various gene editing strategies aimed at enhancing the safety and efficacy of CAR-T cell therapy.
Progress in the study of antibody-drug conjugates for the treatment of cervical cancer
Authors: Zhai Congcong , Cui Yan , Guo Ling , Chen Cixiang , Song Yanfang , Zhong Jinghua , Wang Yili
Published: June 2024

Cervical cancer is the second most prevalent malignancy affecting women’s health globally, and the number of morbidity and mortality from cervical cancer continues to rise worldwide. The 5-year survival rate of patients with recurrent or metastatic cervical cancer is significantly reduced, and existing treatment modalities have low efficacy and high adverse effects, so there is a strong need for new, effective, and well-tolerated therapies. Antibody-drug conjugates (ADCs) are a new targeted therapeutic modality that can efficiently kill tumor cells. This review aims to summarize the composition, research, and development history and mechanism of action of ADCs, to review the research progress of ADCs in the treatment of cervical cancer, and to summarize and prospect the application of ADCs.
Differential expression and clinical significance of long non-coding RNAs in the development and progression of lung adenocarcinoma
Authors: Wei Haitao , Zhang Sa , Lin Xiaojin , Fang Ruirui , Li Li
Published: June 2024

With the development of gene testing technology, we have found many different genes, and lncRNA is one of them. LncRNAs refer to a non-protein coding RNA molecule with a length of more than 200bp, which is one of the focuses of research on human malignant diseases such as LUAD. LncRNAs act as an oncogene or inhibitor to regulate the occurrence and progression of tumors. The differential expression of LncRNAs promotes or inhibits the progression of lung adenocarcinoma by affecting cell proliferation, metastasis, invasion, and apoptosis, thus affecting the prognosis and survival rate of patients. Therefore, LncRNAs can be used as a potential target for diagnosis and treatment of cancer. The early diagnosis of the disease was made through the detection of tumor markers. Because lung adenocarcinoma is not easy to diagnose in the early stage and tumor markers are easy to ignore, LncRNAs play an important role in the diagnosis and treatment of lung adenocarcinoma. The main purpose of this article is to summarize the known effects of LncRNAs on lung adenocarcinoma, the effect of differential expression of LncRNAs on the progression of lung adenocarcinoma, and related signal transduction pathways. And to provide a new idea for the future research of lung adenocarcinoma-related LncRNAs.
Complete elimination of hyperleukocytosis risk in AML through early high-quality disease remission
Authors: Lyu Guoqing , Lyu Wenting
Published: June 2024

Background

Acute myeloid leukemia (AML) with hyperleukocytosis (HL) is a severe medical emergency associated with high mortality rates and poor prognosis. Prompt and urgent treatment is crucial to address this medical emergency. This study aims to elucidate appropriate diagnostic thresholds for HL and investigate underlying mechanisms and potential targeted therapies.

Methods

X-tile software was employed to analyze white blood cell (WBC) count thresholds in AML patients using data from TCGA and TARGET AML databases. METASCAPE and Gene Set Enrichment Analysis (GSEA) were conducted to explore the molecular mechanisms underlying HL in AML. Potential molecular targeted drugs were identified using the CELLMINER platform.

Results

Analysis revealed that a WBC count threshold of 75×109/L, rather than the conventional 100×109/L, is more appropriate for diagnosing HL in adult AML patients. This revised threshold could aid clinicians in identifying a greater number of patients requiring immediate intervention. Significant correlations were observed between HL and specific mutations, including NPM1, FLT3, and DNMT3A. For pediatric AML patients, the HL threshold was determined to be 165×109/L. Achieving complete remission (CR) or deeper levels of remission significantly reduces the risks associated with HL. The reduction in risk can lead to survival outcomes for HL patients that are comparable to those of non-hyperleukocytosis patients. Differential gene expression analysis indicated that downregulation of cell adhesion molecules is implicated in HL pathogenesis. Potential targeted therapies for AML with HL include Bcl2 inhibitors and histone deacetylase inhibitors. Clinical observations demonstrated that the addition of Bcl2 inhibitors, such as Venetoclax, to standard therapy results in a rapid reduction in WBC counts, thereby reducing tumor burden and providing prompt symptom relief. Combining these targeted drugs with conventional therapies appears promising in mitigating risks associated with HL.

Conclusions

Lower diagnostic thresholds for HL in AML, identifies critical genetic correlations, and highlights effective molecular targeted therapies. Proactive early treatment is crucial for achieving deep remission and reducing HL risk. Future therapeutic strategies should consider integrating molecular targeted drugs with conventional therapies to improve outcomes for patients facing this high-risk hematological emergency.