Effects of Different Storage Times on the Stability of 12 Traditional Chinese Medicine Decoction Pieces.

As storage time increases, the quality of traditional Chinese medicines (TCMs) may change, and stability is an essential aspect of ensuring the safety and efficacy of TCMs. In this study, the effects of different storage times on the stability of 12 decoction pieces were evaluated. High-performance liquid chromatography was used to determine the contents of the active components in the 12 decoction pieces. The chemical composition data were analyzed using fingerprinting and clustering heatmap (CH). Results showed that during storage, significant variations (relative standard deviation > 10%) were observed in the levels of paeoniflorin in Paeoniae Radix Alba and Paeoniae Radix Rubra, hesperidin in Citri Reticulatae Pericarpium and Citri Reticulatae Pericarpium Viride, bufothionine in Siccus Bufo and chlorogenic acid in White Chrysanthemi Flos and Lonice Raejaponicae Caulis. However, calycosin-7-glucoside and calycosin in Astragali Radix Praeparata Cum Melle and chlorogenic acid in Lonicerae Japonicae Flos, Yellow Chrysanthemi Flos and Mori Folium were all <10%, which is consistent with the CH. Decoction pieces can be stored for up to six months, but it is recommended that volatile oil-containing and animal-based decoction pieces should not be stored for more than one month. This study provides new perspectives for the stability and quality control studies of TCM.

Application of a feedforward control-based intervention for preventing hypothermia in trauma patients in a pre-hospital emergency setting.

OBJECTIVE: To investigate the efficacy of a feedforward control-based intervention strategy for preventing hypothermia among trauma patients during pre-hospital emergency care. METHODS: We conducted a retrospective analysis comparing trauma patients treated before and after implementing the intervention, with 40 cases in each group. All patients received emergency care from the Fuzhou Emergency Center on the scene. Multivariate analysis was used to explore the risk factors for hypothermia. The effective rate, incidence of adverse reactions, quality of body temperature management, medical staff's knowledge, attitudes, and behaviors regarding mild hypothermia prevention, coagulation function, treatment time at various stages, prognosis score, and treatment situation were compared between the two groups. RESULTS: The adverse reactions, intervention methods, and degree of cognitive improvement were influencing factors for hypothermia. The effective rate (92.50%) in the feedforward control group was higher than that in the non-feedforward control group (65.00%), with a lower incidence of adverse reactions (2.50%). The temperature management quality score of the feedforward control group (6.23±0.62) was higher. The feedforward control group achieved a higher quality score for temperature management (6.23±0.62) and exhibited a greater understanding of hypothermia prevention among trauma patients (P<0.05). Compared to the non-feedforward control group, the feedforward control group showed improved coagulation function, better performance in treatment time at each node, and higher prognosis scores. CONCLUSION: The intervention model based on feedforward control can effectively improve the standard of pre-hospital emergency care and prevent the incidence of hypothermia in trauma patients.

Bioactive peptides in dry-cured ham: A comprehensive review of preparation methods, metabolic stability, safety, health benefits, and regulatory frameworks.

Dry-cured hams contain abundant bioactive peptides with significant potential for the development of functional foods. However, the limited bioavailability of food-derived bioactive peptides has hindered their utilization in health food development. Moreover, there is insufficient regulatory information regarding bioactive peptides and related products globally. This review summarizes diverse bioactive peptides derived from dry-cured ham and by-products originating from various countries and regions. The bioactivity, preparation techniques, bioavailability, and metabolic stability of these bioactive peptides are described, as well as the legal and regulatory frameworks in various countries. The primary objectives of this review are to dig deeper into the functionality of dry-cured ham and provide theoretical support for the commercialization of bioactive peptides from food sources, especially the dry-cured ham.

STAU1 exhibits a dual function by promoting amyloidogenesis and tau phosphorylation in cultured cells.

Staufen-1 (STAU1) is a double-stranded RNA-binding protein (RBP) involved in a variety of pathological conditions. In this study, we investigated the potential role of STAU1 in Alzheimer's disease (AD), in which two hallmarks are well-established as cerebral ß-amyloid protein (Aß) deposition and Tau-centered neurofibrillary tangles. We found that STAU1 protein level was significantly increased in cells that stably express full-length APP and the brain of APP/PS1 mice, an animal model of AD. STAU1 knockdown, as opposed to overexpression, significantly decreased the protein levels of ß-amyloid converting enzyme 1 (BACE1) and Aß. We further found that STAU1 extended the half-life of the BACE1 mRNA through binding to the 3' untranslated region (3'UTR). Transcriptome analysis revealed that STAU1 enhanced the expression of growth arrest and DNA damage 45 ß (GADD45B) upstream of P38 MAPK signaling, which contributed to STAU1-induced regulation of Tau phosphorylation at Ser396 and Thr181. Together, STAU1 promoted amyloidogenesis by inhibiting BACE1 mRNA decay, and augmented Tau phosphorylation through activating GADD45B in relation to P38 MAPK. Targeting STAU1 that acts on both amyloidogenesis and tauopathy may serve as an optimistic approach for AD treatment.

Intestinal microbiota via NLRP3 inflammasome dependent neuronal pyroptosis mediates anxiety-like behaviour in mice exposed to 3.5 GHz radiofrequency radiation.

The rapid development of 5G communication technology has increased public concern about the potential adverse effects on human health. Till now, the impacts of radiofrequency radiation (RFR) from 5G communication on the central nervous system and gut-brain axis are still unclear. Therefore, we investigated the effects of 3.5 GHz (a frequency commonly used in 5G communication) RFR on neurobehavior, gut microbiota, and gut-brain axis metabolites in mice. The results showed that exposure to 3.5 GHz RFR at 50 W/m2 for 1 h over 35 d induced anxiety-like behaviour in mice, accompanied by NLRP3-dependent neuronal pyroptosis in CA3 region of the dorsal hippocampus. In addition, the microbial composition was widely divergent between the sham and RFR groups. 3.5 GHz RFR also caused changes in metabolites of feces, serum, and brain. The differential metabolites were mainly enriched in glycerophospholipid metabolism, tryptophan metabolism, and arginine biosynthesis. Further correlation analysis showed that gut microbiota dysbiosis was associated with differential metabolites. Based on the above results, we speculate that dysfunctional intestinal flora and metabolites may be involved in RFR-induced anxiety-like behaviour in mice through neuronal pyroptosis in the brain. The findings provide novel insights into the mechanism of 5G RFR-induced neurotoxicity.

Short-term regulation of TSFM level does not alter amyloidogenesis and mitochondrial function in type-specific cells.

BACKGROUND: Mitochondrial Ts translation elongation factor (TSFM) is an enzyme that catalyzes exchange of guanine nucleotides. By forming a complex with mitochondrial Tu translation elongation factor (TUFM), TSFM participates in mitochondrial protein translation. We have previously reported that TUFM regulates translation of beta-site APP cleaving enzyme 1 (BACE1) via ROS (reactive oxygen species)-dependent mechanism, suggesting a potential role in amyloid precursor protein (APP) processing associated with Alzheimer's disease (AD), which led to the speculation that TSFM may regulate APP processing in a similar way to TUFM. METHODS AND RESULTS: Here, we report that in cultured cells, knockdown or overexpression TSFM did not change protein levels in BACE1 and APP. Besides, the levels of cytoplasmic ROS and mitochondrial superoxide, in addition to ATP level, cell viability and mitochondrial membrane potential were not significantly altered by TSFM knockdown in the short term. Further transcriptome analysis revealed that expression of majority of mitochondrial genes were not remarkably changed by TSFM silencing. The possibility of TSFM involved in cardiomyopathy and cancer development was uncovered using bioinformatics analysis. CONCLUSIONS: Collectively, short-term regulation of TSFM level in cultured cells does not cause a significant change in proteins involved in APP processing, levels in ROS and ATP associated with mitochondrial function. Whereas our study could contribute to comprehend certain clinical features of TSFM mutations, the roles of TSFM in cardiomyopathy and cancer development might deserve further investigation.

SHMT2 Mediates Small-Molecule-Induced Alleviation of Alzheimer Pathology Via the 5'UTR-dependent ADAM10 Translation Initiation.

It is long been suggested that one-carbon metabolism (OCM) is associated with Alzheimer's disease (AD), whereas the potential mechanisms remain poorly understood. Taking advantage of chemical biology, that mitochondrial serine hydroxymethyltransferase (SHMT2) directly regulated the translation of ADAM metallopeptidase domain 10 (ADAM10), a therapeutic target for AD is reported. That the small-molecule kenpaullone (KEN) promoted ADAM10 translation via the 5' untranslated region (5'UTR) and improved cognitive functions in APP/PS1 mice is found. SHMT2, which is identified as a target gene of KEN and the 5'UTR-interacting RNA binding protein (RBP), mediated KEN-induced ADAM10 translation in vitro and in vivo. SHMT2 controls AD signaling pathways through binding to a large number of RNAs and enhances the 5'UTR activity of ADAM10 by direct interaction with GAGGG motif, whereas this motif affected ribosomal scanning of eukaryotic initiation factor 2 (eIF2) in the 5'UTR. Together, KEN exhibits therapeutic potential for AD by linking OCM with RNA processing, in which the metabolic enzyme SHMT2 "moonlighted" as RBP by binding to GAGGG motif and promoting the 5'UTR-dependent ADAM10 translation initiation.

Percutaneous Intra-arterial Hyaluronidase Injection for Hyaluronic Acid Filler Embolism Threatening Skin Barrier Integrity: Implementation of a Stepwise Treatment Protocol.

BACKGROUND: Hyaluronic acid (HA) filler-induced vascular embolism that threatens skin integrity is an urgent situation. There is increasing evidence that percutaneous intra-arterial hyaluronidase injection is an effective therapeutic technique for it. However, until now, there is a lack of a unifying protocol about the technique. OBJECTIVES: This study aims to provide a conclusion of percutaneous intra-arterial hyaluronidase injection along with adjunctive measures on the treatment of occlusions precipitated by HA-based filler and develop a stepwise treatment protocol. METHODS: We searched PubMed for peer-reviewed studies, consensus statements, case series, and case reports using a variety of keywords. RESULTS: High-dose, pulsed hyaluronidase is the mainstay for the treatment of HA filler-induced embolism, but percutaneous intra-arterial hyaluronidase injection is a more effective technique. Until now, hyaluronidase is injected into three arteries percutaneously, including facial artery, supratrochlear artery, and superficial temporal artery. Furthermore, the adjunctive measures that may optimize clearance of an occlusion and/or skin barrier repair such as the use of image guidance and CGF should be considered. CONCLUSION: Vascular occlusions that threaten skin integrity are an urgent matter which requires accurate diagnosis and effective intervention. Percutaneous intra-arterial hyaluronidase injection along with adjunctive measures performed in a stepwise manner is key to an optimal outcome. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Blinatumomab as bridging therapy in two children with B-cell acute lymphoblastic leukemia complicated by invasive fungal disease]. / 2例急性Bæ·‹å·´ç»†èƒžç™½è¡€ç— åˆå¹¶ä¾µè¢­æ€§çœŸèŒç— å„¿ç«¥åº”ç”¨è´æž—å¦¥æ¬§å•æŠ—æ¡¥æŽ¥æ²»ç–—åˆ†æž.

This article reports two cases of children with B-cell acute lymphoblastic leukemia (B-ALL) complicated by invasive fungal disease (IFD) who received bridging treatment using blinatumomab. Case 1 was a 4-month-old female infant who experienced recurrent high fever and limb weakness during chemotherapy. Blood culture was negative, and next-generation sequencing (NGS) of peripheral blood, bronchoalveolar lavage fluid, and cerebrospinal fluid were all negative. Chest CT and cranial MRI revealed obvious infection foci. Case 2 was a 2-year-old male patient who experienced recurrent high fever with multiple inflammatory masses during chemotherapy. Candida tropicalis was detected in peripheral blood and abscess fluid using NGS, while blood culture and imaging examinations showed no obvious abnormalities. After antifungal and blinatumomab therapy, both cases showed significant improvement in symptoms, signs, and imaging, and B-ALL remained in continuous remission. The report indicates that bridging treatment with blinatumomab in children with B-ALL complicated by IFD can rebuild the immune system and control the underlying disease in the presence of immunosuppression and severe fungal infection.

Simulating immunosuppressive mechanism of Microplitis bicoloratus bracovirus coordinately fights Spodoptera frugiperda.

Parasitoid wasps control pests via a precise attack leading to the death of the pest. However, parasitoid larvae exhibit self-protection strategies against bracovirus-induced reactive oxygen species impairment. This has a detrimental effect on pest control. Here, we report a strategy for simulating Microplitis bicoloratus bracovirus using Mix-T dsRNA targeting 14 genes associated with transcription, translation, cell-cell communication, and humoral signaling pathways in the host, and from wasp extracellular superoxide dismutases. We implemented either one-time feeding to the younger instar larvae or spraying once on the corn leaves, to effectively control the invading pest Spodoptera frugiperda. This highlights the conserved principle of "biological pest control," as elucidated by the triple interaction of parasitoid-bracovirus-host in a cooperation strategy of bracovirus against its pest host.

A Campylobacteriosis Outbreak Caused by One Asymptomatic Food Handler Carrier.

In August 2021, three students with diarrhea from the same school visited a local hospital in the S district of Beijing. An epidemic investigation showed that there were more students with diarrhea in the same school and they had one meal together. Campylobacter jejuni was isolated from both patients with diarrhea and asymptomatic food handlers; however, the latter also carried Campylobacter coli. Phylogenomic analysis showed that there was a campylobacteriosis outbreak among the students, and the asymptomatic food handler may have been the source of the infection. Routine inspection and surveillance for Campylobacter is needed for the food producing staff, particularly those cooking in the cafeteria in schools or other public food services.

Short-term effects of high-resolution (1-km) ambient PM2.5 and PM10 on hospital admission for pulmonary tuberculosis: a case-crossover study in Hainan, China.

Introduction: There is limited evidence regarding particulate matter (PM)'s short-term effects on pulmonary tuberculosis (PTB) hospital admission. Our study aimed to determine the short-term associations of the exposure to ambient PM with aerodynamic diameters <2.5 µm (PM2.5) and < 10 µm (PM10) with hospital admission for PTB in Hainan, a tropical province in China. Methods: We collected individual data on patients hospitalized with PTB, PM2.5, PM10, and meteorological data from 2016 to 2019 in Hainan Province, China. Conditional logistic regression models with a time-stratified case-crossover design were used to assess the short-term effects of PM2.5 and PM10 on hospital admission for PTB at a spatial resolution of 1 km × 1 km. Stratified analyses were performed according to age at admission, sex, marital status, administrative division, and season of admission. Results: Each interquartile range (IQR) increases in the concentrations of PM2.5 and PM10 were associated with 1.155 (95% confidence interval [CI]: 1.041-1.282) and 1.142 (95% CI: 1.033-1.263) hospital admission risks for PTB at lag 0-8 days, respectively. The stratified analyses showed that the effects of PM2.5 and PM10 were statistically significant for patients aged ≥65 years, males, married, and those residing in prefecture-level cities. Regarding seasonal differences, the associations between PM and hospital admission for PTB were statistically significant in the warm season but not in the cold season. The effect of PM2.5 was consistently stronger than that of PM10 in most subgroups. Conclusion: Short-term exposure to PM increases the risk of hospital admission for PTB. The potential impact of PM with smaller aerodynamic diameter is more detrimental. Our findings highlight the importance of reducing ambient PM level to alleviate the burden of PTB.

Genetic and Phenotypic Variation of Campylobacter jejuni NCTC11168 Caused by flhA Mutation during Laboratory Passage.

Objective: Campylobacter jejuni NCTC11168 is commonly used as a standard strain for flagellar biosynthesis research. In this report, two distinguished phenotypic isolates (CJ1Z, flhA mutant strain, lawn; CJ2S, flhA complemented strain, normal colony) appeared during laboratory passages for NCTC11168. Methods: Phenotypic assessments, including motility plates, transmission electron microscopy, biofilm formation assay, autoagglutination assay, and genome re-sequencing for these two isolates (CJ1Z, flhA mutant strain; CJ2S, flhA complemented strain) were carried out in this study. Results: Transmission electron microscopy revealed that the flagellum was lost in CJ1Z. Phenotypic assessments and genome sequencing of the two isolates were performed in this study. The capacity for biofilm formation, colony auto-agglutination, and isolate motility was reduced in the mutant CJ1Z. Comparative genomic analysis indicated a unique native nucleotide insertion in flhA (nt, 2154) that caused the I719Y and I720Y mutations and early truncation in flhA. Conclusion: FlhA has been found to influence the expression of flagella in C. jejuni. To the best of our knowledge, this is the first study to describe the function of the C-terminal of this protein.

[Carbohydrate-based quality consistency evaluation of Saposhnikoviae Radix].

This study aims to evaluate the quality consistency of Saposhnikoviae Radix based on carbohydrates, and explore the potential of carbohydrates as the internal quality control indicators of Saposhnikoviae Radix. The total polysaccharides were quantified by UV-Vis spectrophotometry and the molecular weight range of the polysaccharides was determined by high performance gel-permeation chromatography-evaporative light scattering detection(HPGPC-ELSD). The monosaccharides in polysaccharides and the free monosaccharides were quantified by high performance liquid chromatography-UV detection(HPLC-UV), and the oligosaccharides and fructose were quantified by high performance liquid chromatography-evaporative light scattering detection(HPLC-ELSD). The carbohydrate-based quality of Saposhnikoviae Radix was compared among 45 batches of commercial samples and 13 batches of self-collected samples. The results showed that the molecular weight distribution, monosaccharide composition, oligosaccharide, and free monosaccharide composition were similar in the 58 batches of samples. The average content of total polysaccharides, oligosaccharides, and total free monosaccharides in commercial samples were 39.66, 148.79, and 68.62 mg·g~(-1), respectively. The content showed significant differences among batches, with the highest differences of 3.51, 1.75, and 2.58 times, respectively. The RSD of the relative ratios of monosaccharides in the polysaccharides in commercial samples reached 28%-45%. The average content of total polysaccharides, oligosaccharides, and total free monosaccharides in self-collected samples were 68.07, 145.76, and 42.04 mg·g~(-1), respectively, with the inter-region differences of 2.88, 1.88, and 1.07 times, respectively. The RSD of the relative ratios of monosaccharides in polysaccharides in self-collected samples ranged from 8.2% to 59%. The total polysaccharides and total free monosaccharides in self-collected samples were 1.72 times higher and 1.63 times lower, respectively, than those in commercial samples. The content of oligosaccharides was similar between self-collected samples and commercial samples. To sum up, carbohydrates are one of the material bases for the internal quality consistency of Saposhnikoviae Radix. The qualitative characteristics of polysaccharides and the quantitative characteristics of polysaccharides and oligosaccharides are related to the origin of medicinal materials. Moreover, the quantitative characteristics of polysaccharides and free monosaccharides may be related to the storage conditions. Carbohydrates are potential indicators for the quality control of Saposhnikoviae Radix and deserve attention.

All-trans retinoic acid regulates the expression of MMP-2 and TGF-ß2 via RDH5 in retinal pigment epithelium cells.

AIM: To investigate the effect of all-trans retinoic acid (ATRA) on retinol dehydrogenase 5 (RDH5), matrix metalloproteinase-2 (MMP-2) and transforming growth factor-ß2 (TGF-ß2) transcription levels, and the effect of RDH5 on MMP-2 and TGF-ß2 in retinal pigment epithelium (RPE) cells. METHODS: After adult RPE cell line-19 (ARPE-19 cells) intervened with gradient concentrations of ATRA (0-20 µmol/L) for 24h, flow cytometry was used to detect the proliferation and apoptosis of cells in each group, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect RDH5, MMP-2 and TGF-ß2 mRNA expression. Then, after ARPE-19 cells transfected with three different siRNA targets for 48h, the RDH5 knockdown efficiency of each group and expression of MMP-2 and TGF-ß2 mRNA within them was detected by qRT-PCR. RESULTS: Flow cytometry results showed that ATRA could inhibit the proliferation of RPE cells and promote the apoptosis of RPE cells, and the difference of apoptosis was statistically significant when the ATRA concentration exceeded 5 µmol/L and compared with the normal control group (P=0.027 and P=0.031, respectively). qRT-PCR results showed that ATRA could significantly inhibit the expression level of RDH5 mRNA (P<0.001) and promote the expression of MMP-2 and TGF-ß2 mRNA (P=0.03 and P<0.001, respectively) in a dose-dependent manner, especially when treated with 5 µmol/L ATRA. The knockdown efficiency of RDH5 siRNA varies with different targets, among which RDH5 siRNA-435 had the highest knockdown efficiency, i.e., more than 50% lower than that of the negative control group (P=0.02). When RDH5 was knocked down for 48h, the results of qRT-PCR showed that the expressions of MMP-2 and TGF-ß2 mRNA were significantly up-regulated (P<0.001). CONCLUSION: ATRA inhibits the expression of RDH5 and promotes MMP-2 and TGF-ß2, and further RDH5 knockdown significantly upregulates MMP-2 and TGF-ß2. These findings suggest that RDH5 may be involved in an epithelial-mesenchymal transition of RPE cells mediated by ATRA.

Multimodality US versus Thyroid Imaging Reporting and Data System Criteria in Recommending Fine-Needle Aspiration of Thyroid Nodules.

Background Current guidelines recommend the use of conventional US for risk stratification and management of thyroid nodules. However, fine-needle aspiration (FNA) is often recommended in benign nodules. Purpose To compare the diagnostic performance of multimodality US (including conventional US, strain elastography, and contrast-enhanced US [CEUS]) with the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) in the recommendation of FNA for thyroid nodules to reduce unnecessary biopsies. Materials and Methods In this prospective study, 445 consecutive participants with thyroid nodules from nine tertiary referral hospitals were recruited between October 2020 and May 2021. With univariable and multivariable logistic regression, the prediction models incorporating sonographic features, evaluated with interobserver agreement, were constructed and internally validated with bootstrap resampling technique. In addition, discrimination, calibration, and decision curve analysis were performed. Results A total of 434 thyroid nodules confirmed at pathologic analysis (259 malignant thyroid nodules) in 434 participants (mean age, 45 years ± 12 [SD]; 307 female participants) were included. Four multivariable models incorporated participant age, nodule features at US (proportion of cystic components, echogenicity, margin, shape, punctate echogenic foci), elastography features (stiffness), and CEUS features (blood volume). In recommending FNA in thyroid nodules, the highest area under the receiver operating characteristic curve (AUC) was 0.85 (95% CI: 0.81, 0.89) for the multimodality US model, and the lowest AUC was 0.63 (95% CI: 0.59, 0.68) for TI-RADS (P < .001). At the 50% risk threshold, 31% (95% CI: 26, 38) of FNA procedures could be avoided with multimodality US compared with 15% (95% CI: 12, 19) with TI-RADS (P < .001). Conclusion Multimodality US had better performance in recommending FNA to avoid unnecessary biopsies than the TI-RADS. Clinical trial registration no. NCT04574258 © RSNA, 2023 Supplemental material is available for this article.

ARL6IP1 mediates small-molecule-induced alleviation of Alzheimer pathology through FXR1-dependent BACE1 translation initiation.

Exploring the potential lead compounds for Alzheimer's disease (AD) remains one of the challenging tasks. Here, we report that the plant extract conophylline (CNP) impeded amyloidogenesis by preferentially inhibiting BACE1 translation via the 5' untranslated region (5'UTR) and rescued cognitive decline in an animal model of APP/PS1 mice. ADP-ribosylation factor-like protein 6-interacting protein 1 (ARL6IP1) was then found to mediate the effect of CNP on BACE1 translation, amyloidogenesis, glial activation, and cognitive function. Through analysis of the 5'UTR-targetd RNA-binding proteins by RNA pulldown combined with LC-MS/MS, we found that FMR1 autosomal homolog 1 (FXR1) interacted with ARL6IP1 and mediated CNP-induced reduction of BACE1 by regulating the 5'UTR activity. Without altering the protein levels of ARL6IP1 and FXR1, CNP treatment promoted ARL6IP1 interaction with FXR1 and inhibited FXR1 binding to the 5'UTR both in vitro and in vivo. Collectively, CNP exhibited a therapeutic potential for AD via ARL6IP1. Through pharmacological manipulation, we uncovered a dynamic interaction between FXR1 and the 5'UTR in translational control of BACE1, adding to the understanding of the pathophysiology of AD.

High-frequency repetitive transcranial magnetic stimulation protects against cerebral ischemia/reperfusion injury in rats: Involving the mitigation of ferroptosis and inflammation.

BACKGROUND AND AIM: Repetitive transcranial magnetic stimulation (rTMS) has been found to attenuate cerebral ischemia/reperfusion (I/R) injury. However, its effects and mechanism of action have not yet been clarified. It has been reported that cerebral I/R injury is closely associated not only with ferroptosis but also with inflammation. Hence, the current study aimed to investigate whether high-frequency rTMS attenuates middle cerebral artery occlusion (MCAO)-induced cerebral I/R injury and further to elucidate the mediatory role of ferroptosis and inflammation. METHODS: The protective effects of rTMS on experimental cerebral I/R injury were investigated using transient MCAO model rats. Neurological scores and pathological changes of cerebral ischemic cortex were assessed to evaluate the effects of rTMS on cerebral I/R injury. The involvement of ferroptosis and that of inflammation were examined to investigate the mechanism underlying the effects of rTMS. RESULTS: High-frequency rTMS remarkably rescued the MCAO-induced neurological deficits and morphological damage. rTMS treatment also increased the mRNA and protein expression of glutathione-dependent peroxidase 4, decreased the mRNA and protein levels of acyl-CoA synthetase long-chain family member 4 and transferrin receptor in the cortex. Moreover, rTMS administration reduced the cerebrospinal fluid IL-1ß, IL-6, and TNF-α concentrations. CONCLUSION: These findings implicated that high-frequency rTMS alleviates MCAO-induced cerebral I/R injury, and the underlying mechanism could involve the inhibition of ferroptosis and inflammation. Our study identifies rTMS as a promising therapeutic agent for the treatment of cerebral I/R injury. Moreover, the mechanistic insights into ferroptosis and inflammation advance our understanding of it as a potential therapeutic target for diseases beyond cerebral ischemia stroke.

TNIP2 inhibits amyloidogenesis by regulating the 3'UTR of BACE1: An in vitro study.

TNFAIP3-interacting protein 2 (TNIP2) is known as a negative regulator of NF-κB signaling and inhibit inflammatory response and apoptosis, and is also involved in RNA metabolism. In this study, we investigated the potential role of TNIP2 in amyloidogenesis critically associated with Alzheimer's disease (AD). We found a significant decline of TNIP2 protein level in both mouse and cell model of AD. In SH-SY5Y and HEK cells that stably express human full-length APP695 (SY5Y-APP and HEK-APP), TNIP2 overexpression decreased the protein levels of ß-secretase (BACE1) and C99, as well as Aß peptides (including Aß40 and Aß42), while those of α-secretase (ADAM10) and the related C83 remained unchanged. We further found that TNIP2 promoted the degradation of BACE1 mRNA and was able to bound to the 3' untranslated region (3'UTR) with the reduced luciferase activity. These results indicated that TNIP2 effectively inhibited amyloidogenic processing by regulating the 3'UTR-associated mRNA decay of BACE1.

Solitary bone plasmacytoma of the tibia presenting as chronic osteomyelitis: A rare case report and literature review.

RATIONALE: Plasmacytoma is a rare plasma cell dyscrasia that grows within the axial skeleton or soft tissue structures as solitary or multiple masses. The primary types are solitary plasmacytoma, including solitary bone plasmacytoma (SBP) and solitary extramedullary plasmacytoma, and multiple solitary plasmacytomas. SBP is characterized by localized proliferation of monoclonal plasma cells and is rare. However, SBP with chronic osteomyelitis is even rarer. PATIENT CONCERNS: A 47-year-old man previously diagnosed with chronic osteomyelitis presented with repeated discharge and ulceration in the front of his right tibia. DIAGNOSIS, INTERVENTIONS AND OUTCOMES: Lower extremity magnetic resonance imaging (MRI) and computed tomography (CT) examinations showed dead bone formation and surrounding inflammatory edema. Thus, the patient underwent dead bone excision and fenestration of the bone marrow cavity. The histopathologic examination results indicated plasmacytoma. Therefore, we administered radiotherapy with satisfactory results. LESSONS: Physicians should pay close attention to chronic osteomyelitis because it may be accompanied by plasmacytoma. Postoperative pathological and immunohistochemical examinations are crucial, and surgical resection of the lesion and local radiotherapy are effective treatment methods.