Autoimmune encephalitis related to LGI1 antibodies with negative MRI study: Description of two cases.

BACKGROUND: Leucine-rich glioma inactivated 1 (LGI1) antibody-related autoimmune encephalitis is easily misdiagnosed clinically because of its complex and diverse clinical manifestations. We present two cases of LGI1 antibody-related encephalitis with negative imaging findings and perform a literature review on this disease entity. CASE DESCRIPTION: The first case was that of a 60-year-old man who presented with involuntary movement of the paroxysmal right limb. The second case was that of a 66-year-old man who presented with hearing hallucinations, involuntary shaking of the right limb, and progressive cognitive impairment. Both patients in this study showed negative magnetic resonance imaging (MRI) results. Routine cerebrospinal fluid (CSF) and biochemical examinations showed no significant abnormalities, and positive LGI1 antibodies were detected in both the CSF and serum. CONCLUSION: Based on our experience and the literature review, we recommend that LGI1 antibody-related encephalitis should be considered when faciobrachial dystonic seizures, acute and subacute-onset seizures, low serum sodium (possibly with low CSF chloride), and cognitive-psychiatric disorders are encountered, even in the absence of specific radiographic and altered CSF findings.

Targeting the Immunoglobulin IGSF9 Enhances Antitumor T-cell Activity and Sensitivity to Anti-PD-1 Immunotherapy.

Immune checkpoints modulate the immune response and represent important immunotherapy targets for cancer treatment. However, as many tumors are resistant to current immune checkpoint inhibitors, the discovery of novel immune checkpoints could facilitate the development of additional immunotherapeutic strategies to improve patient responses. Here, we identified increased expression of the adhesion molecule immunoglobulin superfamily member 9 (IGSF9) in tumor cells and tumor-infiltrating immune cells across multiple cancer types. IGSF9 overexpression or knockout in tumor cells did not alter cell proliferation in vitro or tumor growth in immunocompromised mice. Alternatively, IGSF9 deficient tumor cells lost the ability to suppress T-cell proliferation and exhibited reduced growth in immunocompetent mice. Similarly, growth of tumor cells was reduced in IGSF9 knockout syngeneic and humanized mice, accompanied by increased tumor-infiltrating T cells. Mechanistically, the extracellular domain (ECD) of IGSF9 bound to T cells and inhibited their proliferation and activation, and the tumor-promoting effect of IGSF9 ECD was reversed by CD3+ T-cell depletion. Anti-IGSF9 antibody treatment inhibited tumor growth and enhanced the antitumor efficacy of anti-programmed cell death protein 1 immunotherapy. Single-cell RNA sequencing revealed tumor microenvironment remodeling from tumor promoting to tumor suppressive following anti-IGSF9 treatment. Together, these results indicate that IGSF9 promotes tumor immune evasion and is a candidate immune checkpoint target. SIGNIFICANCE: IGSF9 is an immune checkpoint regulator that suppresses T-cell activation in cancer and can be targeted to stimulate antitumor immunity and inhibit tumor growth.

[Temporal Evolution and Source Appointment of Black Carbon Aerosol in Ordos During Summer and Autumn 2019].

In this study, black carbon (BC) aerosols were continuously observed using a seven-channel aethalometer (AE-33) in Ordos from August 12 to October 4, 2019; using this data combined with article matter (PM), pollutant gas, and meteorological element data; a HYSPLIT model; and potential source contribution function (PSCF) and concentration-weighted trajectory (CWT) models, we analyzed the temporal evolution and potential source appointment and main influence areas of BC. The results showed that the average of ρ(BC) was 882 ng·m-3, accounting for 6.08% of PM2.5. The ρ(BC) was mainly concentrated at 200-1000 ng·m-3, accounting for 55.9% of the total samples. In different BC mass concentration ranges, BCliquid was the mainstay, with an average proportion of 86%. The diurnal variations in BC and PM2.5 showed unimodal distributions, with peaks at 08:00 and 10:00, respectively, and peak concentrations increased by 24.3% and 47.2%, respectively. The diurnal variation in BCsolid showed a bimodal distribution, with peaks at 08:00 and 20:00, respectively. The diurnal variation in the BCliquid showed a unimodal distribution with a peak at 08:00. The strong correlation between BC and NO2 indicated a greater impact of vehicle emissions on BC concentration, whereas the weak correlation between BC and SO2 indicated a lower impact of industrial emissions on BC concentration. The dominant air masses affecting the Ordos could be divided into four categories. The southern air masses (35.6%) had the highest mass concentration of atmospheric pollutants, followed by the local air masses (26.9%) and the northwest air masses (18.8%), and the northeast air masses (18.7%) had the lowest mass concentration of pollutants. The influence of the Ordos on the downstream areas was mainly divided into the northeast air masses (40.9%), the northwest air masses (30.4%), and the southeast air masses (28.7%). High CWT value areas of BC were mainly located in the southern Yan'an-Tongchuan-Baoji-Hanzhong areas and Lvliang-Linfen-Sanmenxia-Nanyang areas. They were two long and narrow transmission belts with a weight mass concentration exceeding 1400 ng·m-3. High CWT value areas of BC had the greatest impact on the Wuhai-Bayannaoer-Baotou-Hohhot regions, with a weight concentration exceeding 900 ng·m-3. The long-range transportation of BC could reach the Yulin-Yan'an-Tongchuan-Baoji areas in the south, the Shuozhou-Datong-Beijing areas in the east, and the Xilin Gol League-Xing'an League-Hulunbuir areas in the northeast.

The GLP-1/GIP dual-receptor agonist DA5-CH inhibits the NF-κB inflammatory pathway in the MPTP mouse model of Parkinson's disease more effectively than the GLP-1 single-receptor agonist NLY01.

The GLP-1 receptor agonist exendin-4 has recently shown good effects in a phase II clinical trial in Parkinson's disease (PD) patients. Here, a comparison of the new GLP-1/GIP dual receptor agonist DA5-CH and NLY01, a 40 kDa pegylated form of exendin-4, on motor impairments and reducing inflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD mouse model is provided. The drug groups received either DA5-CH or NLY01 (25 nmol/kg) i.p. after daily MPTP intraperitoneal injection. Both drugs showed improvements in motor activity, open field experiments, rotarod tests, and gait analysis, but DA5-CH was more potent. Tyrosine hydroxylase expression in dopaminergic neurons was much reduced by MPTP and improved by DA5-CH, while NLY01 showed weak effects. When analyzing levels of α-synuclein (α-Syn), DA5-CH reduced levels effectively while NLY01 had no effect. When measuring the levels of the inflammation markers Toll-like receptor 4 (TLR4), specific markers of microglia activation (Iba-1), the marker of astrocyte activation glial fibrillary acidic protein (GFAP), nuclear factor-κB (NF-κB), tumor necrosis factor (TNF-α), and transforming growth factor ß1 (TGF-ß1), DA5-CH was very effective in reducing the chronic inflammation response, while NLY01 did not show significant effects. Levels of key growth factors such as Glial cell-derived neurotrophic factor (GDNF) and Brain-derived neurotrophic factor (BDNF) were much reduced by MPTP, and DA5-CH was able to normalize levels in the brain, while NLY01 showed little effect. The levels of pro-inflammatory cytokines (IL-6 and IL-Iß) were much reduced by DA5-CH, too, while NLY01 showed no effect. In a separate experiment, we tested the ability of the two drugs to cross the blood-brain barrier. After injecting fluorescin-labelled peptides peripherally, the fluorescence in brain tissue was measured. It was found that the pegylated NLY01 peptide did not cross the BBB in meaningful quantities while exendin-4 and the dual agonist DA5-CH did. The results show that DA5-CH shows promise as a therapeutic drug for PD.

[Intervention effects of Zuoguiwan containing serum on osteoblast through ERK1/2 and Wnt/ß-catenin signaling pathway in models with kidney-Yang-deficiency, kidney-Yin-deficiency osteoporosis syndromes].

To clarify the effects of Zuoguiwan containing serum on osteoblast proliferation and alkaline phosphatase(ALP) expression and its effects on the expression of ß-catenin, ERK1, ERK2 mRNA and protein of osteoblast through ERK1/2, Wnt/ß-catenin signaling pathway in models with osteoporosis(OP) kidney-Yang-deficiency, osteoporosis(OP) kidney-Yin-deficiency syndrome. Rat osteoporosis models were established by ovariectomy surgery, and 10 weeks after surgery, hydrocortisone was injected and thyroxine was administered by intragastric administration to establish OP kidney-Yang-deficiency rat model, and OP kidney-Yin-deficiency rat model. Osteoblasts were obtained from 24 h newborn rat skull and were identified by alkaline phosphatase and alizarin red staining. Zuoguiwan containing serum of OP, OP kidney-Yang-deficiency, and OP kidney-Yin-deficiency, as well as the blank serum were used to intervene the osteoblast, and the cells proliferation was detected by MTS. ELISA assay was used to detect ALP expression. RT-PCR assay was used to detect the mRNA expression of ERK1, ERK2, ß-catenin and protein expression levels were detected by Western blot. The results showed that Zuoguiwan containing serum in OP kidney-Yin-deficiency model had stronger effect than OP kidney-Yang-deficiency in promoting osteoblast proliferation, ALP expression, osteoblast ERK1/2, Wnt/ß-catenin signaling pathway related factors ß-catenin, ERK1, ERK2 mRNA and protein expression levels. This was consistent with the TCM theory of "Zuoguiwan nourishes kidney Yin", providing a scientific basis for the clinical and dialectical treatment of osteoporosis. Zuoguiwan could regulate the proliferation and differentiation of bone cells by ERK1/2 and Wnt/ß-catenin signaling pathway, which may be one of the mechanisms of Zuoguiwan for the prevention of osteoporosis.

Variations of human papillomavirus type 58 E6, E7, L1 genes and long control region in strains from women with cervical lesions in Liaoning province, China.

Infection with certain types of human papillomaviruses (HPVs) is a risk factor for the development of cervical cancer. HPV type 58 (HPV 58) is prevalent among Chinese women. The intratype sequence variants differ in oncogenic potential and their prevalences vary across geographic regions. The objective of this study was to analyze the variations of HPV 58 E6, E7, L1 genes and long control region (LCR) in a large samples collected from northeastern Chinese women with cervical lesions. A total of 2938 cervical samples were collected and tested for HPV type using a chip hybridization assay. The E6, E7, L1 genes and LCR of HPV 58 strains were amplified and the amplicons were subjected to direct nucleotide sequencing for variation identification. A total of 235 specimens were HPV 58 positive. High proportions of HPV 58 E6 (83.8%), E7 (76.7%), L1 (90.8%) genes and LCR (91.4%) variants were identified in strains from Chinese women. The most frequently observed variations were C307T (52.4%) in E6, T744G (74.9%) in E7, A6014C (56.9%) in L1 genes and C7266T, A7714G (55.2%) in LCR. For the E6 gene, nine nucleotide variations were identified. Among them, the A140G (T11A), A184C (E25D), G266C (V53L) and A313G were novel variations. Sequencing of the E7 gene revealed four typical nucleotide changes: G761A (G63D), G694A (G41R), T803C (V77A) and T744G. In the L1 gene, 39 nucleotide variations and 13 amino acid substitutions were identified. Among these mutations, 21 variations are reported here for the first time. Lineage A of HPV 58 was found in 142 of 174 strains (81.6%). The most prevalent HPV 58 variants in Chinese northeastern women belongs to lineage A. Novel variations in E6 and L1 genes were also reported. These findings provide new data regarding E6 and L1 gene variations of HPV 58 from women in northeast China.

Genistein synergizes with RNA interference inhibiting survivin for inducing DU-145 of prostate cancer cells to apoptosis.

To further investigate the effect of a combination of genistein with survivin of RNA interference on the proliferation and apoptosis of DU-145 cells, the effect of genistein on the proliferation of DU-145 cells was detected by the MTT method and cytometry, and the apoptosis of cells was observed with fluorescence microscopy. In order to test combined genistein with transfection of small interfering RNA (siRNA) against survivin, a survivin siRNA plasmid was constructed and transfected into DU-145 cells. Genistein inhibited proliferation and induced apoptosis of cancerous DU-145 and Hela cells, whereas genistein had minimal effects for normal L-O2 cells. The stable transfected cell lines of DU-145, knockdown survivin by siRNA, displayed stronger apoptotic than untransfected DU-145, the transfected cell of DU-145 treated with genistein demonstrated the inhibition of proliferation and induction of apoptosis significantly; it showed genistein synergistic effect with RNAi in survivin for inhibition of prostate cancer cells.

A novel protein tyrosine kinase NOK that shares homology with platelet- derived growth factor/fibroblast growth factor receptors induces tumorigenesis and metastasis in nude mice.

Receptor protein tyrosine kinases (RPTKs) play important roles in the regulation of a variety of cellular processes including cell migration, proliferation, and protection from apoptosis. Here, we report the identification and characterization of a novel RPTK-like molecule that has a critical role in induction of tumorigenesis and metastasis and is termed Novel Oncogene with Kinase-domain (NOK). NOK contains a putative single transmembrane domain and a conserved intracellular tyrosine kinase domain that shares homology with members of the platelet-derived growth factor/fibroblast growth factor receptor superfamily. NOK was exclusively located in the cytoplasm. NOK mRNAs were detected in limited human organs and expressed with the highest abundance in the prostate. A variety of tumor cells also expressed the NOK mRNAs. We demonstrated that NIH3T3 and BaF3 cells could be strongly transformed by the expression of the NOK gene as examined by colony formation experiment. In addition, BaF3 cells with the stable expression of NOK induced rapid tumorigenesis in nude mice. Interestingly, these NOK-expressing tumor cells could promptly invade and spread into various distinct organs and form metastatic foci, eventually leading to the rapid death of these animals. Moreover, molecular mechanism studies indicated that NOK could concomitantly activate both MAP kinase and phosphatidylinositol 3'-kinases (PI3K) pathways in stable BaF3 cells. Thus, our results both in vitro and in vivo suggest that NOK is a novel oncogene with the capacity of promoting cell transformation, tumorigenesis, and metastasis.