Neuroprotective Effects of (-)-Epigallocatechin-3-Gallate Against Focal Cerebral Ischemia/Reperfusion Injury in Rats Through Attenuation of Inflammation.

Stroke is the second leading cause of death among adults worldwide. (-)-Epigallocatechin-3-gallate (EGCG) has been demonstrated to exhibit neuroprotective functions in cerebral ischemia/reperfusion injury. However, the underlying mechanisms in this process and its contribution to the protection function remain unknown. The current study examined the neuroprotective effects of EGCG after transient middle cerebral artery occlusion (tMCAO) in rats. tMCAO for 120 min was induced in male Sprague-Dawley rats treated with EGCG (50 mg/kg, i.p.) or Vehicle immediately after reperfusion. Neurological score, infarct ratio and inflammation-related molecules (assessed by 2,3,5-triphenyltetrazolium chloride, enzyme-linked immunosorbent assays, quantitative real-time PCR or western blotting) were estimated at 24 h after operation. EGCG prevented the impairment of neurological function and decreased the infarct volume, compared with the Vehicle group. The inflammation-related molecules TNF-α, IL-1ß, IL-6 levels usually caused by ischemia/reperfusion were significantly ameliorated by EGCG. EGCG also inhibited the upregulation of nuclear factor-kappa B/p65 (NF-κB/p65), and induction of cyclooxygenase 2 and inducible nitric oxide synthase. The present study indicates that EGCG may be a promising therapeutic agent for cerebral ischemia/reperfusion injury through attenuation of inflammation.

Biomaterials as a new option for treating sensorineural hearing loss.

Sensorineural hearing loss (SNHL) usually involves damage to complex auditory pathways such as inner ear cells and auditory nerves. The highly intricate and nuanced characteristics of these cells render their repair and regeneration extremely challenging, making it difficult to restore hearing to normal levels once it has been compromised. The effectiveness of traditional drugs is so minimal that they provide little help with the treatment. Fortunately, extensive experiments have demonstrated that combining biomaterials with conventional techniques significantly enhances drug effectiveness. This article reviews the research progress of biomaterials in protecting hair cells and the auditory nerve, repairing genes related to hearing, and developing artificial cochlear materials. By organizing the knowledge presented in this article, perhaps new insights can be provided for the clinical management of SNHL.

3D printing tissue-engineered scaffolds for auricular reconstruction.

Congenital microtia is the most common cause of auricular defects, with a prevalence of approximately 5.18 per 10,000 individuals. Autologous rib cartilage grafting is the leading treatment modality at this stage of auricular reconstruction currently. However, harvesting rib cartilage may lead to donor site injuries, such as pneumothorax, postoperative pain, chest wall scarring, and deformity. Therefore, in the pursuit of better graft materials, biomaterial scaffolds with great histocompatibility, precise control of morphology, non-invasiveness properties are gradually becoming a new research hotspot in auricular reconstruction. This review collectively presents the exploit and application of 3D printing biomaterial scaffold in auricular reconstruction. Although the tissue-engineered ear still faces challenges before it can be widely applied to patients in clinical settings, and its long-term effects have yet to be evaluated, we aim to provide guidance for future research directions in 3D printing biomaterial scaffold for auricular reconstruction. This will ultimately benefit the translational and clinical application of cartilage tissue engineering and biomaterials in the treatment of auricular defects.

Scd-1 deficiency promotes the differentiation of CD8+ T effector.

The impact of various fatty acid types on adaptive immunity remains uncertain, and their roles remain unelucidated. Stearoyl-CoA desaturase (Scd) is a Δ-9 desaturase, which is a key rate-limiting enzyme for the conversion of saturated fatty acids (SFA) to monounsaturated fatty acids (MUFA) in the fatty acid de novo synthesis. Scd-1 converts stearic acid (SA) and palmitic acid (PA) to oleic acid (OA) and palmitoleic acid (PO), respectively. In this study, through a series of experiments, we showed that Scd-1 and its resulting compound, OA, have a substantial impact on the transformation of CD8+ naïve T cells into effector T cells. Inactivation of Scd-1 triggers the specialization of CD8+ T cells into the Teff subset, enhancing the effector function and mitochondrial metabolism of Teff cells, and OA can partially counteract this. A deeper understanding of lipid metabolism in immune cells and its impact on cell function can lead to new therapeutic approaches for controlling the immune response and improving prognosis.

Rosai-Dorfman Disease of Nasal Soft Tissue: A Case Report.

Rosai-Dorfman disease (RDD) is characterized by sinus histiocytosis with massive lymphadenopathy, and the tissue exhibits positive results for S100 and CD68. This lesion typically affects the lymph nodes and rarely involves the nasal soft tissues. This report aims to present a case of RDD involving the nasal soft tissues, presenting with nasal congestion and rhinorrhea as the primary complaints. The patient underwent surgery navigated by nasal endoscope did not report recurrence after operation.

A Potential Diagnostic and Prognostic Biomarker TMEM176B and Its Relationship With Immune Infiltration in Skin Cutaneous Melanoma.

Background: Melanoma is a highly malignant and aggressive tumor. The search for new and effective biomarkers facilitates early diagnosis and treatment, ultimately improving the prognosis of melanoma patients. Although the transmembrane protein TMEM176B has been linked to a number of cancers, its role in cancer immunity remains unknown. Methods: Expression levels of TMEM176B in normal tissues and several cancers, including Skin Cutaneous Melanoma (SKCM), were collected from TCGA and GTEx. We used Receiver operating characteristic and Kaplan-Meier survival curves and performed regression analysis to elucidate the link between TMEM176B and clinicopathological features of SKCM in order to determine the prognostic significance of TMEM176B in SKCM. We then used the GEPIA and STRING websites to search for proteins and associated top genes that may interact with TMEM176B and enriched them for analysis. The link between TMEM176B and immune cells infiltration was then investigated using TIMER, CIBERSORT algorithm and GSVA package of R (v3.6.3). Finally, animal tests were conducted to confirm the expression of Tmem176b and its influence on T-cell immune infiltration. Results: TMEM176B expression was considerably elevated in SKCM compared to normal tissues. Particularly, TMEM176B expression was also linked to pathological stage, tumor ulceration and radiation therapy. Patients with elevated TMEM176B expression had a better prognosis, according to the survival analysis. The majority of tumor infiltrating lymphocytes (TILs) especially T cells in SKCM was positively linked with TMEM176B expression. Our animal experiments also verified that the T-cell infiltration was significantly inhibited in local melanoma tissue of Tmem176b knockout mice. At the same time deleting Tmem176b accelerated tumor progress and impaired T cells effector function. Conclusion: Upregulated expression of TMEM176B in SKCM is associated with a better prognosis and it has the potential to serve as a diagnostic and prognostic marker for the disease. It may serve as a target for SKCM immunotherapy by regulating CD8+ T cells although it requires more evidence.

FAT1 and MSH2 Are Predictive Prognostic Markers for Chinese Osteosarcoma Patients Following Chemotherapeutic Treatment.

Osteosarcoma is characterized by diverse genetic mutations, including single-nucleotide variants (SNVs), which can complicate clinical outcomes of the treatment. This study identified key mutations or polymorphisms in genes that correlate with osteosarcoma prognoses. A total of 110 patients with osteosarcoma were assigned to "good" or "poor" cohorts depending on their 5-year disease-free survival (DFS) after surgery and chemotherapeutic treatment. We performed next-generation sequencing analysis of tumor tissues for prognosis-associated SNVs in 315 tumorigenesis-related genes, followed by modeling of clinical outcomes for these patients using random forest classification via a support vector machine (SVM). Data from the Chinese Millionome Database were used to compare SNV frequency in osteosarcoma patients and healthy people. SVM screening identified 17 nonsynonymous SNVs located in 15 genes, of which rs17224367 and rs3733406 (located in MSH2 and FAT1, respectively) were strongly correlated with osteosarcoma prognosis. These results were verified in a 26-patient validation cohort, confirming that these SNVs could be used to predict prognosis. These results demonstrated that two SNVs located in MSH2 and FAT1 are associated with prognosis of osteosarcoma patients. © 2022 American Society for Bone and Mineral Research (ASBMR).

Targeting T cell metabolism for immunotherapy.

T cells play an important role in antitumor immunity. Numbers and function of T cells are controlled by regulating the uptake and utilization of nutrients, and their antitumor activity can be promoted by targeting metabolic pathways. In this review, we highlight the relationship between metabolism and cellular function of T cells. Specifically, we emphasize the metabolic state of tumor-infiltrating T cells and review key pathways that affect the antitumor function of T cells. In the field of tumor immunotherapy, targeting T cell metabolism to enhance the immune response is a new therapeutic strategy for enhancing immunotherapy combined with traditional treatments.

Neuroinflammation in Alzheimer's disease.

Amyloid-ß plaques and neurofibrillary tangles are the main neuropathological hallmarks in Alzheimer's disease (AD), the most common cause of dementia in the elderly. However, it has become increasingly apparent that neuroinflammation plays a significant role in the pathophysiology of AD. This review summarizes the current status of neuroinflammation research related to AD, focusing on the connections between neuroinflammation and some inflammation factors in AD. Among these connections, we discuss the dysfunctional blood-brain barrier and alterations in the functional responses of microglia and astrocytes in this process. In addition, we summarize and discuss the role of intracellular signaling pathways involved in inflammatory responses in astrocytes and microglia, including the mitogen-activated protein kinase pathways, nuclear factor-kappa B cascade, and peroxisome proliferator-activated receptor-gamma transcription factors. Finally, the dysregulation of the control and release of pro- and anti-inflammatory cytokines and classic AD pathology (amyloid plaques and neurofibrillary tangles) in AD is also reviewed.

[The preparation and identification of rabbit's antibody of chymopapain].

Chymopapain, one of the four cysteine proteinases of papaya latex, has milk clotting and proteolytic activity. It is mainly used to treat prolapsed intervertebral discs. This paper introduced the preparation of polyclonal antibody of partially purified chymopapain and the identification of the antibody specificity. The polyclonal antibody provides a basis for the further researches and applications of chymopapain.

[Killing effect of Ad.TERT-TRAIL on tumor cell lines and its mechanism].

BACKGROUND & OBJECTIVE: Oncolytic adenovirus Ad.TERT, a novel tumor-specific proliferating virus, has been constructed by replacing normal promoter of mild-type adenovirus E1A with promoter of human telomerase reverse transcriptase (hTERT). In vitro and in vivo experiments confirmed that Ad.TERT has antitumor effect. This study was to construct Ad.TERT-TRAIL through inserting apoptosis gene trail into Ad.TERT, and explore its antitumor effect and mechanism. METHODS: Plasmid pZhTERT-trail and adenovirus packaging plasmid pBHGE3 were homologously recombined in HEK293 cells to construct Ad.TERT-TRAIL. Ad.TERT-TRAIL was identified by polymerase chain reaction (PCR), and confirmed by Western blot. Killing effects of Ad.TERT-TRAIL and Ad.TERT on 3 tumor cell lines, SW620, BEL-7404 and Bcap-37, and a normal cell line NHLF were detected by crystal violet dye method or MTT assay. Expression of Caspase-3 in Ad.TERT-TRAIL-, and Ad.TERT-transfected SW620 cells was detected by Western blotu cell apoptosis was detected by flow cytometry (FCM). RESULTS: The 860 bp-length trail gene has been amplified by PCR. Western blot showed trail and E1A only expressed in tumor cells, which confirmed the successful construction of Ad.TERT-TRAIL. Killing effects of Ad.TERT-TRAIL on tumor cells were 10-100 times as strong as that of Ad.TERTu while both of them had little effects on normal cells. After 3 days infection (100 multiple of infection, MOI), survival rate of Ad.TERT-TRAIL-infected SW620 cells was 4%, but that of Ad.TERT-infected SW620 cells was 56%u both viruses had little effects on NHLF cells. Expression of Caspase-3 was higher in Ad.TERT-TRAIL-infected SW620 cells than in Ad.TERT-infected SW620 cells. Apoptosis rate of Ad.TERT-TRAIL-infected SW620 cells was 4 times as high as that of Ad.TERT-infected SW620 cells. CONCLUSIONS: Ad.TERT-TRAIL has much stronger antitumor effect than Ad.TERT. Its effect might relate with inducement effects of trail gene on expression of Caspase-3, and apoptosis of tumor cells.