Structural characteristics, biological activities and market applications of Rehmannia Radix polysaccharides: A review.

Rehmannia Radix Polysaccharides (RRPs) are biopolymers that are isolated and purified from the roots of Rehmannia glutinosa Libosch, which have attracted considerable attention because of their biological activities, such as anti-inflammatory, antioxidant, immunomodulatory, anti-tumor, hypoglycaemic etc. In this manuscript, the composition and structural characteristics of RRPs are reviewed. Moreover, the research progress on the conformational relationships and biological activities of RRPs is systematically summarized. Additionally, this manuscript also analyzes 155 patents using RRPs as the main raw materials to explore the status quo and bottleneck for the development and utilization of RRPs. In summary, this review not only provides a theoretical basis for future research on RRPs but also provides clear guidance for their market applications and innovation.

Intelligent drugs based on notch protein remodeling: a defensive targeting strategy for tumor therapy.

In the process of tumor treatment, systemic drug administration is hindered by biological barriers, leading to the retention of a large number of drug molecules in healthy tissues and causing unavoidable side effects. The precise deployment of drugs at the tumor site is expected to alleviate this phenomenon. Here, we take endostatin and Her2 (+) tumors as examples and develop an intelligent drug with simple "wisdom" by endowing mesenchymal stem cells (MSCs) with an intelligent response program (iMSCEndostatin). It can autonomously perceive and distinguish tumor cells from non-tumor cells, establishing a logical connection between tumor signals and drug release. Enable it to selectively deploy drugs at the tumor site, thereby locking the toxicity of drugs at the tumor site. Unlike traditional aggressive targeting strategies that aim to increase drug concentration at the lesion, intelligent drugs are more inclined to be defensive strategies that prevent the presence of drugs in healthy tissues.

Solution NMR backbone resonance assignment of the full-length resistance-related calcium-binding protein Sorcin.

Sorcin is a penta-EF hand calcium-binding protein that confers multidrug resistance in cancer cells. It regulates cellular Ca2+ homeostasis by interacting with calcium channels such as Ryanodine receptor 2 and Sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in a calcium-dependent manner. The crystal structure of the Sorcin has been determined in both calcium-free and calcium-bound states to understand calcium-binding induced conformational change. However, due to its flexibility, most of the N-terminal domain is invisible in these crystal structures. Here we report the 1H, 13C, and 15N backbone resonance assignments of full-length Sorcin in the calcium-free state using solution NMR. The protein secondary structure was predicted based on the assigned backbone chemical shifts using TALOS+ and CSI 3.0. Our backbone resonance assignment of the full-length Sorcin provides a foundation for future NMR spectroscopic studies to uncover the mechanism of Ca2+ sensing by Sorcin.

High-dose-rate brachytherapy in uterine cervix carcinoma: a comparison of dosimetry and clinical outcomes among three fractionation schedules.

Background: To assess the differences among three dose-fractionation schedules of image-guided adaptive brachytherapy (IGABT) in cervical squamous cell carcinoma (CSCC) by comparing the dosimetry and clinical outcomes. Methods: Forty-five patients with CSCC who underwent chemoradiotherapy and IGABT were retrospectively enrolled and divided into three groups based on their dose-fractionation schedules of brachytherapy as: Group-5.5 (5.5 Gy × 6 fractions), Group-6.0 (6.0 Gy × 5 fractions), and Group-7.0 (7.0 Gy × 4 fractions). The analyzed dose-volume histogram parameters included D90% and D98% of the high-risk clinical target volume (HR-CTV), D90% and D98% of intermediate-risk clinical target volume (IR-CTV), and D0.1cc and D2cc of the organs-at-risk (OARs, namely the bladder, rectum, sigmoid and small intestine). Furthermore, the therapeutic efficacy and late toxicities were also compared among the three groups. Results: The doses of HR-CTV and IR-CTV in Group-5.5 were found to be the highest among the three groups, followed by those in Group-6.0. Significant differences were found for the doses of HR-CTV between Group-5.5 and the other groups. There were no significant differences in the bladder, sigmoid and small intestine dose among the three groups. However, Group-6.0 yielded the lowest rectum received doses, with a significant difference in D0.1cc being detected between Group-6.0 and Group-5.5. The median follow-up time was 30.08 months [range, 6.57-46.3]. The numbers of patients with complete response in Group-5.5, Group-6.0 and Group-7.0 were 13, 14 and 14, respectively (P > 0.05). In regard to the toxicitiy, the incidence of radiation cystitis and proctitis in Group-6.0 was lower than that in Group-5.5 and Group-7.0 (P > 0.05). Conclusions: The dose-fractionation schedule of 6.0 Gy × 5 fractions provided the most beneficial effects with relatively low OARs doses, suggesting that this dose-fractionation schedule should be prioritized in the clinical application of brachytherapy in cervical cancer.

An artificial signaling pathway primitive-based intelligent biomimetic nanoenzymes carrier platform for precise treatment of Her2 (+) tumors.

In tumor treatment, the deposition of nanoenzymes in normal tissues and cause potential side effects are unavoidable. Here, we designed an intelligent biomimetic nanoenzymes carrier platform (MSCintelligent) that endows the carrier platform with "wisdom" by introducing Affibody-Notch(core)-VP64-GAL4/UAS-HSV-TK artificial signal pathways to mesenchymal stem cells (MSCs). This intelligent nanoenzymes carrier platform is distinguished from the traditional targeting tumor microenvironment or enhancing affinity with tumor, which endue MSCintelligent with tumor signal recognition capacity, so that MSCintelligent can autonomously distinguish tumor from normal tissue cells and feedback edited instructions. In this study, MSCintelligent can convert tumor signals into HSV-TK instructions through artificial signal pathway after recognizing Her2 (+) tumor. Subsequently, the synthesized HSV-TK can rupture MSCintelligent under the mediation of ganciclovir, and release the preloaded Cu/Fe nanocrystal clusters to kill the tumor accurately. Meanwhile, MSCintelligent without recognizing tumors will not initiate the HSV-TK instructions, thus being unresponsive to GCV and blocking the release of nanoenzymes in normal tissues. Consequently, MSCintelligent is the first intelligent biomimetic nanoenzymes carrier platform, which represents a new biomimetic nanoenzymes targeting mode.

Enhanced therapeutic potential of Flotillins-modified MenSCs by improve the survival, proliferation and migration.

Menstrual blood-derived endometrial stem cells (MenSCs) have attracted increasing interest due to their excellent safety, and lack of ethical dilemma as well as their ability to be periodically obtained in a noninvasive manner. However, although preclinical research as shown the therapeutic potential of MenSCs in several diseases, their poor cell survival and low engraftment at disease sites reduce their clinical efficacy. Flotillins (including Flot1 and Flot2) are implicated in various cellular processes, such as vesicular trafficking, signal transduction, cell proliferation, migration and apoptosis. In this study, we aimed to determine the effects of Flotillins on MenSCs survival, proliferation and migration. Our experimental results show that MenSCs were modified to overexpress Flot1 and/or Flot2 without altering their intrinsic characteristics. Flot1 and Flot2 co-overexpression promoted MenSC viability and proliferation capacity. Moreover, Flot1 or Flot2 overexpression significantly promoted the migration and inhibited the apoptosis of MenSCs compared with the negative control group, and these effects were stronger in the Flot1 and Flot2 gene co-overexpression group. However, these effects were significantly reversed after Flot1 and/or Flot2 knockdown. In conclusion, our results indicate that Flot1 and Flot2 overexpression in MenSCs improved their proliferation and migration and inhibited their apoptosis, and this might be an effective approach to improve the efficiency of cell-based therapies.

CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation.

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.

Role and molecular mechanism of NOD2 in chronic non-communicable diseases.

Nucleotide-binding oligomerization domain containing 2 (NOD2), located in the cell cytoplasm, is a pattern recognition receptor belonging to the innate immune receptor family. It mediates the innate immune response by identifying conserved sequences in bacterial peptide glycans and plays an essential role in maintaining immune system homeostasis. Gene mutations of NOD2 lead to the development of autoimmune diseases such as Crohn's disease and Blau syndrome. Recently, NOD2 has been shown to be associated with the pathogenesis of diabetes, cardiac-cerebral diseases, and cancers. However, the function of NOD2 in these non-communicable diseases (CNCDs) is not well summarized in reviews. Our report mainly discusses the primary function and molecular mechanism of NOD2 as well as its potential clinical significance in CNCDs.

Hawthorn Fruit (Crataegus spp.) Polysaccharides Exhibit Immunomodulatory Activity on Macrophages via TLR4/NF-κB Signaling Activation.

The immunostimulatory effects and the involved molecular mechanisms of polysaccharides from hawthorn fruit (Crataegus spp.) have not been well understood. In this study, the chemical composition, monosaccharide composition, uronic acid content, and structural features of hawthorn fruit polysaccharides (HFP) and the two collected fractions were analyzed. Both AF1-2 and AF2 have pectic-like structural features rich in galacturonic acid. AF2 showed superior proinflammatory effects on macrophages which significantly increased the secretion of pro-inflammatory cytokines interleukin-1ß, interleukin-6, and tumor necrosis factor-α, but not AF1-2. AF2 was found to activate the nuclear factor-κB signaling pathway with suppressed expression of IκBα but up-regulated expression of p-IκBα and nuclear factor-κB P65. The surface binding site of AF2 on macrophage cells was characterized and toll like receptor-4 was responsible for AF2 induced activation of down-stream nuclear factor-κB signaling pathways. AF2 from hawthorn fruit could be potentially used as a natural source of immunomodulator in functional foods.

[Research progress on structure, structure-activity relationship, and biological activity of Aconiti Lateralis Radix Praeparata polysaccharides].

Aconiti Lateralis Radix Praeparata polysaccharides(AP) are a class of bioactive macromolecules extracted from the herbs of Aconiti Lateralis Radix Praeparata and its various processed products. Since the AP was first separated in 1986, its pharmacological effects include immune regulation, anti-tumor, anti-depression, organ protection, hypoglycemia, and anti-inflammatory had been found. In recent years, with the development of polysaccharide extraction, separation, and structure identification technologies, more than 20 kinds of AP have been separated from Aconiti Lateralis Radix Praeparata and its processed products, and they have ob-vious differences in relative molecular weight, monosaccharide composition, glycosidic bond, structural characteristics, and biological activities. In particular, AP may be dissolved, degraded, or allosteric under the complex processing environment of fermentation, soaking, cooking, etc., leading to the diversified structure of AP, which provides a possibility for further understanding of the structure-activity relationship of AP. Therefore, this study systematically reviewed the research progress on the structure and structure-activity relationship of AP, summarized the biological activity and potential action mechanism of AP, and discussed the technical challenges in the development and application of AP, so as to promote the quality control and further development and utilization of AP.

Acquired resistance to KRAS G12C small-molecule inhibitors via genetic/nongenetic mechanisms in lung cancer.

Inherent or acquired resistance to sotorasib poses a substantialt challenge for NSCLC treatment. Here, we demonstrate that acquired resistance to sotorasib in isogenic cells correlated with increased expression of integrin ß4 (ITGB4), a component of the focal adhesion complex. Silencing ITGB4 in tolerant cells improved sotorasib sensitivity, while overexpressing ITGB4 enhanced tolerance to sotorasib by supporting AKT-mTOR bypass signaling. Chronic treatment with sotorasib induced WNT expression and activated the WNT/ß-catenin signaling pathway. Thus, silencing both ITGB4 and ß-catenin significantly improved sotorasib sensitivity in tolerant, acquired, and inherently resistant cells. In addition, the proteasome inhibitor carfilzomib (CFZ) exhibited synergism with sotorasib by down-regulating ITGB4 and ß-catenin expression. Furthermore, adagrasib phenocopies the combination effect of sotorasib and CFZ by suppressing KRAS activity and inhibiting cell cycle progression in inherently resistant cells. Overall, our findings unveil previously unrecognized nongenetic mechanisms underlying resistance to sotorasib and propose a promising treatment strategy to overcome resistance.

High-Quality Indigo Naturalis Obtained with Automatic Foam Separation.

Indigo Naturalis is not only an ancient plant dye but also a famous herbal medicine with antibacterial, anti-inflammatory, and anticancer properties. In traditional processes, thousands of manual stirring separate the high-quality Indigo Naturalis from the crude pulp system. However, this method is time-consuming and labor-intensive, resulting in an unstable quality and low yield, which cannot meet the requirements of modern industrial production. In this study, foam-separation technology was used to increase the industrial applicability of high-quality Indigo Naturalis. The process parameters were optimized based on the content of active ingredients, skin irritation effects, and antioxidative stress activity. The results showed that the optimal process of the foam separation achieved the liquid level difference of 40 cm and the foaming intensity of 0.35 MPa. Compared with the original sample, the indigo and indirubin contents in purified Indigo Naturalis were 1.6 and 3 times higher, the total ash content decreased from 86 to 70%, the pH value decreased from 12.18 to 9.71, and the leachate doubled. Animal experiments suggested the significantly reduced irritation (p < 0.01) and enhanced antioxidative stress activity (p < 0.01) of Indigo Naturalis after foam separation. Therefore, the foam-separation equipment developed in this study enabled the refinement of active ingredients in Indigo Naturalis, which greatly improved the production efficiency and quality.

[Physicochemical properties and anti-inflammatory and immunomodulatory effects of Shengfupian polysaccharides].

In this study, the crude polysaccharides was extracted from Shengfupian and purified by Sevag deproteinization. Then, the purified neutral polysaccharide fragment was obtained by the DEAE-52 cellulose chromatography column and Sephadex G-100 co-lumn. The structure of polysaccharides was characterized by ultraviolet spectroscopy, infrared spectroscopy, ion chromatography, and gel permeation chromatography. To investigate the anti-inflammatory activity of Shengfupian polysaccharides, LPS was used to induce inflammation in RAW264.7 cells. The expression of the CD86 antibody on surface of M1 cells, the function of macrophages, and the content of NO and IL-6 in the supernatant were examined. An immunodepression model of H22 tumor-bearing mice was established, and the immunomodulatory activity of Shengfupian polysaccharides was evaluated based on the tumor inhibition rate, immune organ index and function, and serum cytokine levels. Research indicated that Shengfupian polysaccharides(80 251 Da) was composed of arabinose, galactose, glucose, and fructose with molar ratio of 0.004∶0.018∶0.913∶0.065. It was smooth and lumpy under the scanning electron microscope. In the concentration range of 25-200 µg·mL~(-1), Shengfupian polysaccharides exhibited little or no toxicity to RAW264.7 cells and could inhibit the polarization of cells to the M1 type and reduce the content of NO and IL-6 in the cell supernatant. It could suppress the phagocytosis of cells at the concentration of 25 µg·mL~(-1), while enhancing the phagocytosis of RAW264.7 cells within the concentration range of 100-200 µg·mL~(-1). The 200 mg·kg~(-1) Shengfupian polysaccharides could alleviate the spleen injury caused by cyclophosphamide, increase the levels of IL-1ß and IL-6, and decrease the level of TNF-α in the serum of mice. In conclusion, Shengfupian polysaccharides has anti-inflammatory effect and weak immunomodulatory effect, which may the material basis of Aconm Lateralis Radix Praeparaia for dispelling cold and relieving pain.

COVID-19-related secretory otitis media in the omicron era: a case series.

OBJECTIVES: Increased numbers of patients with secretory otitis media appeared in outpatient clinics after the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron pandemic; however, the relationship between SARS-CoV-2 Omicron variant infection and secretory otitis media is uncertain. METHODS: We performed tympanocentesis and used reverse transcription-polymerase chain reaction (RT-PCR) testing to examine middle ear effusion (MEE) and nasopharyngeal secretions from 30 patients with secretory otitis media associated with SARS-CoV-2 infection. RT-PCR was performed using the open reading frame 1ab and nucleocapsid protein gene kit from Shanghai Berger Medical Technology Co., Ltd., as the sole assay method, in accordance with the manufacturer's instructions. RESULTS: MEEs from 5 of the 30 patients tested positive for SARS-CoV-2, including one patient with positive results for both the nasopharyngeal secretion and MEE. We report and discuss the medical records of six patients, including these five MEE-positive patients and a MEE-negative patient. CONCLUSION: SARS-CoV-2 RNA can be detected in MEE caused by coronavirus disease 2019-related secretory otitis media even when a patient's nasopharyngeal secretion tests PCR-negative for SARS-CoV-2. The virus can remain in the MEE for a long time after SARS-CoV-2 infection.

Conditioned medium of human menstrual blood-derived endometrial stem cells protects against cell inflammation and apoptosis of Npc1KO N2a cells.

Niemann-Pick disease type C1 (NPC1) is a hereditary neurodegenerative disorder caused by a mutation in the NPC1 gene. This gene encodes a transmembrane protein found in lysosomes. This disease characterized by hepatosplenomegaly, neurological impairments and premature death. Recent preclinical studies have shown promising results in using mesenchymal stem cells (MSCs) to alleviate the symptoms of NPC1. One type of MSCs, known as human menstrual blood-derived endometrial stem cells (MenSCs), has attracted attention due to its accessibility, abundant supply, and strong proliferation and regeneration capabilities. However, it remains uncertain whether the conditioned medium of MenSCs (MenSCs-CM) can effectively relieve the symptoms of NPC1. To investigate this further, we employed the CRISPR-Cas9 technique to successfully create a Npc1 gene knockout N2a cell line (Npc1KO N2a). Sanger sequencing confirmed the occurrence of Npc1 gene mutation in these cells, while western blotting revealed a lack of NPC1 protein expression. Filipin staining provided visual evidence of unesterified cholesterol accumulation in Npc1KO N2a cells. Moreover, Npc1KO N2a cells exhibited significantly decreased viability, increased inflammation, and heightened cell apoptosis. Notably, our study demonstrated that the viability of Npc1KO N2a cells was most significantly improved after being cultured by 36 h-collected MenSCs-CM for 0.5 days. Additionally, MenSCs-CM exhibited the ability to effectively reduce inflammation, counteract cell apoptosis, and ameliorate unesterified cholesterol accumulation in Npc1KO N2a cells. This groundbreaking finding establishes, for the first time, the protective effect of MenSCs-CM on N2a cells with Npc1 gene deletion. These findings suggest that the potential of MenSCs-CM as a beneficial therapeutic approach for NPC1 and other neurodegenerative diseases.

Promotion of BST2 expression by the transcription factor IRF6 affects the progression of endometriosis.

Background: Endometriosis (EM) is a benign, multifactorial, immune-mediated inflammatory disease that is characterized by persistent activation of the NF-κB signaling pathway and some features of malignancies, such as proliferation and lymphangiogenesis. To date, the pathogenesis of EM is still unclear. In this study, we investigated whether BST2 plays a role in the development of EM. Methods: Bioinformatic analysis was performed with data from public databases to identify potential candidate targets for drug treatment. Experiments were conducted at the cell, tissue, and mouse EM model levels to characterize the aberrant expression patterns, molecular mechanisms, biological behaviors of endometriosis as well as treatment outcomes. Results: BST2 was significantly upregulated in ectopic endometrial tissues and cells compared with control samples. Functional studies indicated that BST2 promoted proliferation, migration, and lymphangiogenesis and inhibited apoptosis in vitro and in vivo. The transcription factor (TF) IRF6 induced high BST2 expression by directly binding the BST2 promoter. The underlying mechanism by which BST2 functions in EM was closely related to the canonical NF-κB signaling pathway. New lymphatic vessels may serve as a channel for the infiltration of immune cells into the endometriotic microenvironment; these immune cells further produce the proinflammatory cytokine IL-1ß, which in turn further activates the NF-κB pathway to promote lymphangiogenesis in endometriosis. Conclusion: Taken together, our findings provide novel insight into the mechanism by which BST2 participates in a feedback loop with the NF-κB signaling pathway and reveal a novel biomarker and potential therapeutic target for endometriosis.

The protective effect and antitumor activity of Aconiti Lateralis Radix Praeparata (Fuzi) polysaccharide on cyclophosphamide-induced immunosuppression in H22 tumor-bearing mice.

Background: Aconiti Lateralis Radix Praeparata, also known as Fuzi in Chinese, has been used in Traditional Chinese Medicine for more than 2,000 years. In recent years, some traditional herbal compounds containing Fuzi have achieved positive clinical results in tumor treatment. And the polysaccharide isolated from Fuzi has attracted much attention as a potential immunomodulator. However, its immunomodulatory mechanism remains to be further studied. Aim of the study. Fuzi neutral polysaccharide (FNPS) and cyclophosphamide (CTX) were combined to treat Hepatoma 22 (H22) tumor-bearing mice, and its mechanism of ameliorating immunosuppression caused by CTX was studied. Methods: FNPS was isolated and purified. The molecular weight, functional groups, monosaccharide composition, and apparent morphology were characterized by gel permeation chromatography, Fourier transform infrared spectrometer, ion chromatography and scanning electron microscope, respectively. Through the analysis of tumor, immune organs, and serum cytokine levels of H22 tumor-bearing mice, the immunomodulatory effect and the protective effect on immunosuppressive mice induced by CTX was evaluated. And the immunomodulatory activity of FNPS was further verified by macrophage functional experiments. Results: FNPS was composed of rhamnose, arabinose, galactose, glucose, and mannose in a molar ratio of 0.008:0.017:0.018:0.908:0.048. Its molecular weight was 94 kDa. In vivo experiments showed that 200 mg mL-1 FNPS could alleviate the suppression of immune organs and immune cells caused by CTX treatment, enhance the antitumor effect of CTX, increase the serum levels of Th1 immune-related pro-inflammatory cytokines (IL-1ß and IL-6), and decrease Th2 immune-related anti-inflammatory cytokine (IL-10) and tumor-related pro-inflammatory cytokine (TNF-α) in the chemotherapy mice. Functional experiments revealed that 25 µg mL-1 FNPS could promote phagocytosis and proliferation of macrophages. When the concentration reached 50 µg mL-1, it enhanced the migration activity. Conclusion: FNPS has the potential to alleviate the immunosuppressive effect of CTX by activating immune cells and promoting inflammation. It could be used as a potential auxiliary medication for liver cancer treatment.

Menstrual blood-derived endometrial stem cells inhibit neuroinflammation by regulating microglia through the TLR4/MyD88/NLRP3/Casp1 pathway.

Neuroinflammation is a common response in various neurological disorders. Mesenchymal stem cell-based treatment has become a promising therapy for neuroinflammation-associated diseases. However, the effects of mesenchymal stem cells are controversial, and the underlying mechanism is incompletely understood. In the present study, menstrual blood-derived endometrial stem cells were intravenously transplanted into a mouse model of neuroinflammation established by peripheral injection of lipopolysaccharide. Microglial cells challenged with lipopolysaccharide were cultured with conditioned medium from endometrial stem cells. The levels of cytokines were detected by enzyme-linked immunosorbent assay. Cell proliferation and death were detected by Cell Counting Kit 8 and flow cytometry, respectively. The expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), NLR family pyrin domain containing 3 (NLRP3) and caspase 1 (Casp1) were evaluated by western blotting. The results showed that intravenous transplantation of endometrial stem cells downregulated proinflammatory factors and upregulated anti-inflammatory factors in the brain of mice with neuroinflammation. Conditioned medium suppressed the inflammatory reaction and hyperactivation of microglial cells and protected microglial cells from cell death induced by lipopolysaccharide in vitro. The expression of TLR4, MyD88, NLRP3 and Casp1 in the brain of mice with neuroinflammation and in lipopolysaccharide-stimulated microglial cells was downregulated by endometrial stem cells and conditioned medium, respectively. These data suggested that menstrual blood-derived endometrial stem cells may suppress neuroinflammatory reactions partially by regulating microglia through the TLR4/MyD88/NLRP3/Casp1 signalling pathway. Our findings may be very useful for the development of an alternative stem cell-based therapy for neuroinflammation-associated disorders.

Identification and Analysis of Potential Immune-Related Biomarkers in Endometriosis.

Background: Endometriosis is an inflammatory gynecological disease leading to deep pelvic pain, dyspareunia, and infertility. The pathophysiology of endometriosis is complex and depends on a variety of biological processes and pathways. Therefore, there is an urgent need to identify reliable biomarkers for early detection and accurate diagnosis to predict clinical outcomes and aid in the early intervention of endometriosis. We screened transcription factor- (TF-) immune-related gene (IRG) regulatory networks as potential biomarkers to reveal new molecular subgroups for the early diagnosis of endometriosis. Methods: To explore potential therapeutic targets for endometriosis, the Gene Expression Omnibus (GEO), Immunology Database and Analysis Portal (ImmPort), and TF databases were used to obtain data related to the recognition of differentially expressed genes (DEGs), differentially expressed IRGs (DEIRGs), and differentially expressed TFs (DETFs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DETFs and DEIRGs. Then, DETFs and DEIRGs were further validated in the external datasets of GSE51981 and GSE1230103. Then, we used quantitative real-time polymerase chain reaction (qRT-PCR) to verify the hub genes. Simultaneously, the Pearson correlation analysis and protein-protein interaction (PPI) analyses were used to indicate the potential mechanisms of TF-IRGs at the molecular level and obtain hub IRGs. Finally, the receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of the hub IRGs. Results: We screened a total of 94 DETFs and 121 DEIRGs in endometriosis. Most downregulated DETFs showed decreased expression in the endometria of moderate/severe endometriosis patients. The top-ranked upregulated DEIRGs were upregulated in the endometra of infertile women. Functional analysis showed that DETFs and DEIRGs may be involved in the biological behaviors and pathways of endometriosis. The TF-IRG PPI network was successfully constructed. Compared with the control group, high C3, VCAM1, ITGB2, and C3AR1 expression had statistical significance in endometriosis among the hub DEIRGs. They also showed higher sensitivity and specificity by ROC analysis for the diagnosis of endometriosis. Finally, compared with controls, C3 and VCAM1 were highly expressed in endometriosis tissue samples. In addition, they also showed high specificity and sensitivity for diagnosing endometriosis. Conclusion: Overall, we discovered the TF-IRG regulatory network and analyzed 4 hub IRGs that were closely related to endometriosis, which contributes to the diagnosis of endometriosis. Additionally, we verified that DETFs or DEIRGs were associated with the clinicopathological features of endometriosis, and external datasets also confirmed the hub IRGs. Finally, C3 and VCAM1 were highly expressed in endometriosis tissue samples compared with controls and may be potential biomarkers of endometriosis, which are helpful for the early diagnosis of endometriosis.

Isolated splenic metastases from rectal carcinoma 5 years after surgery: Case report.

INTRODUCTION: Splenic malignancies are mostly lymphocytic tumors and splenic metastases are rarer.[1] According to reports, the most common source of splenic metastases include melanoma, tumors of the breast, lung, ovary, colon, stomach, and pancreas.[2,3]. PATIENT CONCERNS: This paper reports a 41-year-old male patient who underwent a successful resection of low rectal cancer in our hospital 5 years ago. DIAGNOSIS: Three months ago, computed tomography scan revealed a tumor in the spleen, considered as an isolated metastasis. INTERVENTIONS: The patient underwent splenectomy and postoperative pathological examination confirmed metastatic adenocarcinoma. OUTCOMES: The patient was followed up for 3 months after surgery, there was no abdominal metastasis or recurrence. CONCLUSION: The splenic metastasis from rectal carcinoma 5 years after surgery is rare. If it is a solitary splenic metastasis, splenectomy can effectively improve the prognosis of patients. We review the literature and report this case.