Protein Levels Research Articles

Nutritional, Anti-Nutritional and Sensory Evaluation of Snacks Produced from Germinated Maize/Bambara Groundnut (Vigna Subterranean) Flours

Background: Bambara nut, an underutilized legume is rich in protein and can improve the nutritional quality of snacks. This study evaluates the nutritional and sensory properties of muffins produced from germinated maize and Bambara groundnut flours. Methods: Maize and Bambara groundnut seeds were germinated (72 hours), oven-dried and milled. The composite flours from the germinated flours were combined with soya oil, tiger-nut milk, date and carrot powder to produce four samples of muffins. The samples were chemically analyzed for proximate, mineral, beta-carotene, and anti-nutrient contents. Then, sensory evaluation was carried out among 20 mothers (20-30) using a 5 hedonic scale. ANOVA and Duncan Multiple Range Test were also used to analyze the data. Results: Protein, fiber and carbohydrate contents of the muffins ranged from 7.63-9.23%, 0.05-0.08% and 70.63-71.55%, respectively. It was found that germination significantly increased protein and iron content of muffins but reduced zinc, calcium, and beta-carotene contents (P<0.001). The muffins contributed above 22% of the RDA regarding energy for children. Muffins produced from the blends provided higher level of protein, calcium, iron and beta-carotene compared to those made from whole wheat flour. There was a significant reduction in anti-nutrient contents of the muffins and germinated flours. The muffin produced from the 80% maize and 20% Bambara nut flour was rated best in terms of nutritional value, taste, and texture. Conclusion: Bambara nut flours could be used to produce nutritious snacks which would contribute to daily energy and protein needs of children.

Comprehensive analysis of CXCL10 and MIP-3a reveals their potential clinical application in hepatocellular carcinoma

Chemokines play a crucial role in the pathogenesis of patients with hepatocellular carcinoma (HCC). The expression levels of interferon-γ-induced protein-10 (CXCL10) and macrophage inflammatory protein-3α (MIP-3a) were investigated to clarify their clinical significance in HCC.The protein levels of CXCL10 and MIP-3a in the serum of 105 HBV-associated HCC patients, 50 patients with liver cirrhosis (LC), 50 patients with chronic hepatitis B (CHB) and 50 healthy donors (HC) were detected by liquid chip technology (Luminex) or ELISA. In addition, their mRNA levels were also determined in liver cancer and adjacent cancer tissue (paracancer; ParaCa) from 65 HCC patients. The online database UALCAN was used to analyze the association between CXCL10 and pathological manifestations of liver cancer. In addition, the diagnostic value of CXCL10/MIP-3a and AFP in HCC patients was determined by analyzing the Receiver Operating Characteristic Curve (ROC).The protein concentrations of CXCL10 and MIP-3a were significantly higher in the HCC group than in the LC, CHB and HC groups. CXCL10 in sera and liver cancer tissues is significantly positively correlated with ALT, but no significance between CXCL10 in ParaCa tissues and sera-ALT. Their mRNA is significantly higher in cancer tissues than in ParaCa tissues. The areas under the ROC curve of CXCL10, MIP-3a, CXCL10 and MIP-3a combined and AFP were 0.9169, 0.9261, 0.9299 and 0.7880, respectively. Elevated chemokines CXCL10 and MIP-3a in HCC patients may be associated with the clinical manifestation of HCC and could be a potential molecular marker for prognostic evaluation or a therapeutic target for HCC.

New-onset of giant cell arteritis with ischemic optic neuropathy following the seventh-dose of COVID-19 mRNA vaccination: A case report and literature review.

Coronavirus disease (COVID-19) vaccines have demonstrated excellent efficacy in reducing the morbidity and severity of the disease. However, some patients have been reported to develop systemic rheumatic diseases, such as rheumatoid arthritis, myocarditis, Guillain-Barre syndrome, and giant cell arteritis (GCA) following COVID-19 vaccination. We present a case of GCA with ischemic optic neuropathy following COVID-19 mRNA vaccination. A 73-year-old woman developed headache, myalgia, scalp tenderness, and jaw claudication 4 days after her seventh dose of the vaccination; she also developed severe visual disturbances 1 month after the vaccination. The blood examination tests showed an increased serum C-reactive protein level and erythrocyte sedimentation rate. The echogram for the temporal artery showed a halo sign. Ophthalmic examination revealed ischemic optic neuropathy in both eyes. The patient was treated with a high-dose glucocorticoid and tocilizumab under the diagnosis of GCA with ischemic optic neuropathy, obtaining mild improvement of the symptoms. This report underscores the need for clinical vigilance and further data collection regarding GCA cases after COVID-19 vaccination.

A testis-specific lncRNA functions as a post-transcriptional regulator of MDM2 and stimulates apoptosis of testicular germ cell tumor cells

Germ cells preferentially induce apoptosis in response to DNA damage to avoid genomic mutations. Apoptosis of germ cells is closely related to cancer development and chemotherapy resistance; however, its regulatory mechanism is unclear. Here, we suggest that testis-specific lncRNA LINC03074 is involved in male germ cell apoptosis by regulating the expression of the proto-oncogene MDM2. LINC03074 is highly expressed in the sperm of healthy adult testes and cancer cells of testes with testicular germ cell tumors (TGCTs). LINC03074 binds to MDM2 mRNA via an Alu element, thereby reducing MDM2 protein levels. LINC03074 stimulates STAU1-mediated nuclear export of MDM2 mRNA by increasing STAU1 binding to MDM2 mRNA in the cell nucleus, thereby promoting PKR-mediated translational repression in the cytoplasm. The induction of apoptosis in TGCT cells and their responsiveness to the anticancer drug cisplatin is enhanced by LINC03074. Notably, LINC03074 increased E2F1 expression without increasing p53, the primary target of MDM2, and upregulated the apoptotic gene p73, the target gene of E2F1. LINC03074-mediated regulation of apoptosis contributes to the responsiveness of TGCTs to anticancer drug-induced DNA damage.

Intranasal AdipoRon Mitigated Anxiety and Depression-Like Behaviors in 6-OHDA-Induced Parkinson 's Disease Rat Model: Going Beyond Motor Symptoms.

Depression and anxiety are prevalent neuropsychiatric conditions among patients with Parkinson's disease (PD), which may manifest prior to motor symptoms. As levodopa, a prominent treatment for PD motor symptoms, provides few benefits for mood-related abnormalities, tackling non-motor symptoms is particularly important. AdipoRon (Ad), an adiponectin agonist, has demonstrated neuroprotective effects by suppressing neuroinflammatory responses and activating the AMPK/Sirt-1 signaling pathway. This study looked at the potential advantages and underlying mechanisms of intranasal Ad in a rat model of PD induced by 6-hydroxydopamine (6-OHDA). We found that Ad at doses of 1 and 10µg for 21 days exhibited anxiolytic- and antidepressant effects in the open field (OF) test, elevated plus maze (EPM), sucrose splash test, and forced swimming test in a PD model caused by a unilateral 6-OHDA injection into the medial forebrain bundle (MFB). The Ad also lowered the levels of corticosterone in the blood, decreased inflammasome components (NLRP3, caspase 1, and IL-1β), and increased Sirt-1 protein levels in the prefrontal cortex (PFC) of PD rats. We conclude that Ad ameliorates anxious and depressive-like behaviors in the PD rat model through stimulating the AMPK/Sirt-1 signaling and blocking the NLRP3 inflammasome pathways in the PFC.

Toxicity and safety of rosemary (Rosmarinus officinalis): a comprehensive review.

Rosemary (Rosmarinus officinalis) contains alkaloids, phenolic acids, saponins, tannins, diterpenes, flavonoids, and essential oils and has antioxidant, anti-inflammatory, antibacterial, anticancer, neuroprotective, cardioprotective, and hepatoprotective effects. While rosemary is generally considered safe for consumption and topical application, allergic reactions and dermatitis have been reported in some individuals. This paper provides an in-depth review of the current studies on rosemary toxicity, shedding light on its potential adverse effects and underlying mechanisms. Google Scholar, PubMed, Scopus, and Web of Science were used to perform extensive research from the inception of these databases until February 2024. The toxicological effects explored include affecting several organs such as the liver and kidney by causing atrophic and degenerative changes, increasing blood urea nitrogen (BUN), aspartate aminotransferase (AST), and reducing total serum protein levels. Rosemary may induce reproductive toxicity by decreasing spermatogenesis in the testes, testosterone, sperm density, and motility. It might also trigger genotoxicity and anomalies in fetuses by increasing cytoplasmic membrane shrinkage, the formation of apoptotic bodies, internucleosomal deoxyribonucleic acid (DNA) fragmentation, and DNA ladder formation. While rosemary is considered safe for food preservation, caution is warranted regarding chronic and high doses due to potential adverse effects on the kidneys, liver, reproductive system, and teratology. Additionally, it underscores the significance of considering drug interactions. The article also highlights the importance of considering toxicological data in realistic exposure situations and discusses the relevance of these findings for human health. Hence, further research is recommended to enhance our understanding of the toxicity profile associated with rosemary.

Hansenula polymorpha methanol metabolism genes enhance recombinant protein production in Komagataella phaffi

Recombinant protein production in Komagataella phaffi (K. phaffi), a widely utilized host organism, can be optimized by enhancing the metabolic flux in the central carbon metabolism pathways. The methanol utilization pathway (MUT) during methanol-based growth plays a crucial role in providing precursors and energy for cell growth and development. This study investigated the impact of boosting the methanol dissimilation pathway, a branch of MUT that plays a vital role in detoxifying formaldehyde and providing energy in the form of NADH, in K. phaffi. This was achieved by integrating two orthologous genes from Hansenula polymorpha into the K. phaffi genome: formaldehyde dehydrogenase (HpFLD) and formate dehydrogenase (HpFMDH). The HpFLD and HpFMDH genes were isolated from the Hansenula polymorpha genome and inserted under the regulation of the pAOX1 promoter in the genome of recombinant K. phaffi that already contained a single copy of model protein genes (eGFP or EGII). The expression levels of these model proteins were assessed through protein activity assays and gene expression analysis. The findings revealed that while both orthologous genes positively influenced model protein production, HpFMDH exhibited a more pronounced upregulation in expression compared to HpFLD. Co-expression of both orthologous genes demonstrated synergistic effects, resulting in approximately a twofold increase in the levels of the model proteins detected. This study provides valuable insights into enhancing the production capacity of recombinant proteins in K. phaffi.Graphical abstract

The analysis on Tiam2 for expression in esophageal carcinoma: A descriptive study.

To investigate T lymphoma invasion and metastasis inducing factor 2 (Tiam2) protein for expression in esophageal carcinoma and relationship with clinical features among cases with tumors. In primary esophageal cancer patients, surgical resection of tumor tissue was performed in 65 cases and adjacent normal esophageal tissue in 20 cases. Primary esophageal carcinoma (57 cases squamous cell carcinoma, 8 cases adenosquamous carcinoma). The expression level of Tiam2 protein in esophageal carcinoma tissues and normal esophageal tissues by SP immunohistochemical method. The expression intensity was quantitatively analyzed by using Image-pro plus software for image analysis, while SPSS26.0 software was used for a statistical analysis on the data. Tiam2 was highly expressed in esophageal squamous cell carcinoma and adenosquamous cell carcinoma, but low expressed in normal esophageal tissue. The expression level of Tiam2 protein was not correlated with gender and age of patients (P > .05), but was correlated with lymph node metastasis of esophageal carcinoma, TNM stage and differentiation degree of esophageal squamous cell carcinoma (P < .05). Tiam2 was positively correlated with Tiam1 for protein expression in esophageal carcinoma (r = .704, P < .001). The increased expression of Tiam2 protein in esophageal cancer may be an early molecular event of esophageal cancer. Tiam2 protein has a high expression level in esophageal carcinoma related to lymph node metastasis, TNM stage and differentiation degree, which suggests that Tiam2 protein plays an important role in the invasion and metastasis of esophageal carcinoma. There is a positive correlation between Tiam2 and Tiam1 protein expressions in esophageal carcinoma, suggesting that the 2 proteins may have a definite internal relationship.

Efficacy and safety of first-line anti-tuberculosis drugs combined with Linezolid for the treatment of pediatric tuberculous meningitis in real-word practice

Objective: To evaluate the efficacy and safety of first-line anti-tuberculosis (TB) drugs combined with linezolid in treatment of children with tuberculous meningitis (TBM). Methods: A retrospective cohort study design was performed. Eight-nine Children diagnosed as TBM during January 1st 2016 and December 31st 2023 in Department of Infectious Disease, Children's Hospital of Chongqing Medical University were enrolled in the study. According to different treatment regimens, children were divided into a group of first-line anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE)) and a group of HRZE and linezolid combination (HRZEL). The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed. Comparisons between groups were performed using χ2 test and Mann-Whitney U test. Results: The 89 children with TBM included 53 males and 36 females with an onset age of 4.6 (1.4, 9.6) years. There were 27 cases in the HZREL group and 62 cases in the HRZE group. Before treatment, positive rate of interferon-gamma release assays (IGRA) in HRZEL group was lower than that in HRZE group (64% (16/25) vs.92% (55/60), χ2=9.82, P<0.05), but protein level of cerebrospinal fluid (CSF) was higher than that in HRZE group (1.2 (1.0, 2.0) vs.0.8 (0.4,1.4) g/L, Z=0.32, P<0.05). By the end of the intensive phase, there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group (both P>0.05).The 44 TBM children with high CSF protein (>1 g/L) included 25 males and 19 females with an onset age of 6.7 (3.0, 11.8) years. There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly. Before treatment, there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups (62% (13/21) vs. 87% (20/23), 1.7 (1.1, 2.2) vs. 1.5 (1.2, 1.9) g/L, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions: The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.

Multiplex Sensing of Biomarkers on the Cancer Cell Surface by an Epithelial-Mesenchymal Transition (EMT) Sensing Panel Enables Precise Differentiating of Cancer Cells at Various EMT Stages.

Epithelial-mesenchymal transition (EMT) is a complex process that plays a critical role in tumor progression. In this study, we present an EMT sensing panel for the classification of cancer cells at different EMT stages. This sensing panel consists of three types of fluorescent probes based on boronic acid-functionalized carbon-nitride nanosheet (BCN) derivatives. The selective response toward different EMT-associated biomarkers, namely, EpCAM, N-cadherin, and sialic acid (SA), was achieved by conjugating the corresponding antibodies to each BCN derivative, whereas the rare-earth-doping ensures simultaneous sensing of the three biomarkers with fluorescent emission of the three probes at different wavelengths. Sensitive sensing of the three biomarkers was achieved at the protein level with LODs reaching 1.35 ng mL-1 for EpCAM, 1.62 ng mL-1 for N-cadherin, and 1.54 ng mL-1 for SA. The selective response of these biomarkers on the cell surface also facilitated sensitive detection of MCF-7 cells and MDA-MB-231 cells with LODs of 2 cells/mL and 2 cells/mL, respectively. Based on the simultaneous sensing of the three biomarkers on cancer cells that underwent different extents of EMT, precise discrimination and classification of cells at various EMT stages were also achieved with an accuracy of 93.3%. This EMT sensing panel provided a versatile tool for monitoring the EMT evolution process and has the potential to be used for the evaluation of the EMT-targeting therapy and metastasis prediction.

Dissection of the synthesis of polyunsaturated fatty acids in nematodes and Collembola of the soil fauna

It is becoming increasingly clear that not only unicellular, photoautotrophic eukaryotes, plants, and fungi, but also invertebrates are capable of synthesizing ω3 long-chain polyunsaturated fatty acids (LC-PUFA) de novo. However, the distribution of this anabolic capacity among different invertebrate groups and its implementation at the gene and protein level are often still unknown. This study investigated the PUFA pathways in common soil fauna, i.e. two nematode and two Collembola species. Of these, one species each (Panagrellus redivivus, Folsomia candida) was assumed to produce ω3 LC-PUFA de novo, while the others (Acrobeloides bodenheimeri, Isotoma caerulea) were supposed to be unable to do so. A highly labeled oleic acid (99 % 13C) was supplemented and the isotopic signal was used to trace its metabolic path. All species followed the main pathway of lipid biosynthesis. However, in A. bodenheimeri this terminated at arachidonic acid (ω6 PUFA), whereas the other three species continued the pathway to eicosapentaenoic acid (ω3 PUFA), including I. caerulea. For the nematode P. redivivus the identification and functional characterization of four new fatty acid desaturase (FAD) genes was performed. These genes encode the FAD activities Δ9, Δ6, and Δ5, respectively. Additionally, the Δ12 desaturase was analyzed, yet the observed activity of an ω3 FAD could not be attributed to a coding gene. In the Collembola F. candida, 11 potential first desaturases (Δ9) and 13 front-end desaturases (Δ6 or Δ5 FADs) have been found. Further sequence analysis indicates the presence of omega FADs, specifically Δ12, which are likely derived from Δ9 FADs.

Ultrasound-stimulated microbubbles enhances radiosensitivity in cervical cancer

Background Ultrasound-stimulated microbubble (USMB) therapy has proven efficacy of targeting tumor vasculature and enhancing the effect of radiation in tumor xenografts. In this investigation, we studied whether this treatment enhances the sensitivity of cervical cancer to radiation. Methods Human cervical cancer (ME-180 and SiHa) cells were treated with USMB or exposed to radiation (0, 2, 4, 6 and 8 Gy) or radiation (8 Gy) in combination with USMB. Clone formation assay and CCK-8 assay were used to analyze the proliferation capacity of cells. Apoptosis and DNA double-strand breaks were detected using flow cytometry and immunofluorescence staining of gamma-H2AX (γ-H2AX), respectively. Matrigel tubule formation was performed to evaluate the angiogenesis of human umbilical vein endothelial cells. In xenograft model of SiHa cells, tumor tissue expression of CD31 was detected by immunohistochemistry. Results USMB and radiation synergistically restrained the growth of ME-180 and SiHa cells. USMB promoted radiation-induced apoptosis by enhancing the levels of proapoptotic proteins. Furthermore, USMB enhanced radiation-induced γ-H2AX foci to induce DNA double-strand breaks in cervical cancer cells. USMB in combination with radiation reduced the angiogenic capacity of endothelial cells in vitro. Moreover, USMB strengthened the inhibitory effect of radiation on tumor growth and angiogenesis in xenograft models. Conclusion In conclusion, USMB exposure effectively enhanced the destructive effect of radiation on cervical cancer, suggesting that USMB might be a promising sensitizer of radiotherapy to treat cervical cancer.

Multiomics to Characterize the Molecular Events Underlying Impaired Glucose Tolerance in FXR-Knockout Mice.

The prevalence of different metabolic syndromes has grown globally, and the farnesoid X receptor (FXR), a metabolic homeostat for glucose, lipid, and bile acid metabolisms, may serve an important role in the progression of metabolic disorders. Glucose intolerance by FXR deficiency was previously reported and observed in our study, but the underlying biology remained unclear. To investigate the ambiguity, we collected the nontargeted profiles of the fecal metaproteome, serum metabolome, and liver proteome in Fxr-null (Fxr-/-) and wild-type (WT) mice with LC-HRMS. FXR deficiency showed a global impact on the different molecular levels we monitored, suggesting its serious disruption in the gut microbiota, hepatic metabolism, and circulating biomolecules. The network and enrichment analyses of the dysregulated metabolites and proteins suggested the perturbation of carbohydrate and lipid metabolism by FXR deficiency. Fxr-/- mice presented lower levels of hepatic proteins involved in glycogenesis. The impairment of glycogenesis by an FXR deficiency may leave glucose to accumulate in the circulation, which may deteriorate glucose tolerance. Lipid metabolism was dysregulated by FXR deficiency in a structural-dependent manner. Fatty acid β-oxidations were alleviated, but cholesterol metabolism was promoted by an FXR deficiency. Together, we explored the molecular events associated with glucose intolerance by impaired FXR with integrated novel multiomic data.

Heat-killed probiotic Levilactobacillus brevis MKAK9 and its exopolysaccharide promote longevity by modulating aging hallmarks and enhancing immune responses in Caenorhabditis elegans

BackgroundProteostasis is a critical aging hallmark responsible for removing damaged or misfolded proteins and their aggregates by improving proteasomal degradation through the autophagy-lysosome pathway (ALP) and the ubiquitin–proteasome system (UPS). Research on the impact of heat-killed probiotic bacteria and their structural components on aging hallmarks and innate immune responses is scarce, yet enhancing these effects could potentially delay age-related diseases.ResultsThis study introduces a novel heat-killed Levilactobacillus brevis strain MKAK9 (HK MKAK9), along with its exopolysaccharide (EPS), demonstrating their ability to extend longevity by improving proteostasis and immune responses in wild-type Caenorhabditis elegans. We elucidate the underlying mechanisms through a comprehensive approach involving mRNA- and small RNA sequencing, proteomic analysis, lifespan assays on loss-of-function mutants, and quantitative RT-PCR. Mechanistically, HK MKAK9 and its EPS resulted in downregulation of the insulin-like signaling pathway in a DAF-16-dependent manner, enhancing protein ubiquitination and subsequent proteasomal degradation through activation of the ALP pathway, which is partially mediated by microRNA mir-243. Importantly, autophagosomes engulf ubiquitinylated proteins, as evidenced by increased expression of the autophagy receptor sqst-3, and subsequently fuse with lysosomes, facilitated by increased levels of the lysosome-associated membrane protein (LAMP) lmp-1, suggesting the formation of autolysosomes for degradation of the selected cargo. Moreover, HK MKAK9 and its EPS activated the p38 MAPK pathway and its downstream SKN-1 transcription factor, which are known to regulate genes involved in innate immune response (thn-1, ilys-1, cnc-2, spp-9, spp-21, clec-47, and clec-266) and antioxidation (sod-3 and gst-44), thereby reducing the accumulation of reactive oxygen species (ROS) at both cellular and mitochondrial levels. Notably, SOD-3 emerged as a transcriptional target of both DAF-16 and SKN-1 transcription factors.ConclusionOur research sets a benchmark for future investigations by demonstrating that heat-killed probiotic and its specific cellular component, EPS, can downregulate the insulin-signaling pathway, potentially improving the autophagy-lysosome pathway (ALP) for degrading ubiquitinylated proteins and promoting organismal longevity. Additionally, we discovered that increased expression of microRNA mir-243 regulates insulin-like signaling and its downstream ALP pathway. Our findings also indicate that postbiotic treatment may bolster antioxidative and innate immune responses, offering a promising avenue for interventions in aging-related diseases.

Association between high-sensitivity C-reactive protein and renal function in Korean adults: A sex-specific analysis of Korea National Health and Nutrition Examination Survey 2015 to 2018 data.

This study aimed to investigate the association between high-sensitivity C-reactive protein (hs-CRP) levels, as a surrogate marker of systemic inflammation, and renal function among Korean adults grouped by age, sex, and body mass index. This study analyzed data obtained from the Korea National Health and Nutrition Examination Survey 2015 to 2018, a cross-sectional and nationally representative survey conducted by the Korean Centers for Disease Control and Prevention. Of the 22,451 subjects included in this study, 19,607 (87.3%) and 2844 (12.7%) had normal kidney function and incident chronic kidney disease, respectively. Reduced renal function was more frequently observed in subjects with high hs-CRP levels than in those with low hs-CRP levels (odds ratio [OR], 1.438; 95% confidence interval [CI], 1.234-1.674). In the group aged ≥ 65 years, the odds of reduced renal function were higher among subjects with a high hs-CRP level compared to those with a low hs-CRP level (OR, 1.528; 95% CI, 1.191-1.960). The association between hs-CRP level and renal function was observed only in women (OR, 2.485; 95% CI, 1.779-3.470) and further stratified by age and sex, the odds of reduced renal function were likely higher in women aged ≥ 65 years with a high hs-CRP level (OR, 2.338; 95% CI, 1.622-3.369). Moreover, reduced renal function was more observed in subjects aged ≥ 65 years and those with a body mass index < 25 kg/m2 (OR, 1.502; 95% CI, 1.087-2.075). This study showed that a high hs-CRP level likely contributes to the increased prevalence of reduced renal function. This association may aid the identification of individuals at high risk for reduced renal function, especially elderly women, in clinical or public health practice.

The Complex Relationship between Neuromodulators, Circadian Rhythms, and Insomnia in Patients with Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) has been linked to disruptions in circadian rhythm and neurotrophin (NFT) signaling. This study explored the link between neuromodulators, chronotype, and insomnia in OSA. The participants (n = 166) underwent polysomnography (PSG) before being categorized into either the control or the OSA group. The following questionnaires were completed: Insomnia Severity Index (ISI), Epworth Sleepiness Scale, Chronotype Questionnaire (morningness-eveningness (ME), and subjective amplitude (AM). Blood samples were collected post-PSG for protein level assessment using ELISA kits for brain-derived neurotrophic factor (BDNF), proBDNF, glial-cell-line-derived neurotrophic factor, NFT3, and NFT4. Gene expression was analyzed utilizing qRT-PCR. No significant differences were found in neuromodulator levels between OSA patients and controls. The controls with insomnia exhibited elevated neuromodulator gene expression (p &lt; 0.05). In the non-insomnia individuals, BDNF and NTF3 expression was increased in the OSA group compared to controls (p = 0.007 for both); there were no significant differences between the insomnia groups. The ISI scores positively correlated with all gene expressions in both groups, except for NTF4 in OSA (R = 0.127, p = 0.172). AM and ME were predicting factors for the ISI score and clinically significant insomnia (p &lt; 0.05 for both groups). Compromised compensatory mechanisms in OSA may exacerbate insomnia. The correlation between chronotype and NFT expression highlights the role of circadian misalignments in sleep disruptions.

YiQi GuBen formula alleviates airway inflammation and airway remodeling in OVA-induced asthma mice through TLR4/NF-κB signaling pathway.

We aim to investigate the effect of YiQi GuBen formula (YQGB) on airway inflammation and airway remodeling in the ovalbumin (OVA)-induced asthma model to further explore the potential mechanisms of YQGB in treating allergic asthma. Mice were divided into five groups randomly (n = 10): the control group, OVA group, OVA + Dex (0.1 mg/kg) group, OVA + low-dose (1.1 g/kg) YQGB group, and OVA + high-dose (2.2 g/kg) YQGB group. Inflammatory cell count and IgE were detected in bronchoalveolar lavage fluid (BALF). Lung tissue histopathology was observed by using H&E, PAS, Masson, and immunohistochemistry staining. qRT-PCR and western blot were applied to analyze key genes and proteins associated with TLR4 and NF-κB signaling pathways. In OVA-induced asthma mice, YQGB decreased eosinophils and IgE in BALF. YQGB alleviated the OVA-induced inflammatory infiltration and declined IL-4, IL-5, IL-13, Eotaxin, ECP, GM-CSF, LTC4, and LTD4. YQGB attenuated the OVA-induced goblet cell metaplasia and mucus hypersecretion. YQGB mitigated the OVA-induced subepithelial fibrosis and lowered TGF-β1, E-Cadherin, Vimentin, and Fibronectin. YQGB ameliorated the OVA-induced airway smooth muscle thickening and lessened α-SMA and PDGF levels. YQGB reduced the expression of TLR4, MyD88, TRAF6, IκBα, and p65 mRNAs, and IκBα and p-p65 protein levels were also reduced. YQGB exhibits the anti-asthma effect by reducing airway inflammation and airway remodeling through suppressing TLR4/NF-κB signaling pathway, and is worth promoting clinically.

Clinical efficacy of one-stage anterior debridement and bone graft fusion for the treatment of cervical pyogenic spondylodiscitis

Objective: To investigate the efficacy of one-stage anterior debridement and bone graft fusion for the treatment of cervical pyogenic spondylodiscitis. Methods: This is a retrospective case series study. Retrospective analysis of clinical data from 23 patients with cervical pyogenic spondylodiscitis treated with one-stage anterior approach debridement and bone graft fusion was performed in the Department of Spinal Surgery, the First Affiliated Hospital of Xinjiang Medical University from January 2015 to January 2020. There were 14 males and 9 females,aged (51.9±12.8) years (range:26 to 82 years). Preoperatively, 14 patients had neurological deficits, classified according to the American Spinal Injury Association (ASIA) impairment scale as follows: grade A in 1 case, grade B in 1 case, grade C in 5 cases, and grade D in 7 cases. All patients underwent the one-stage anterior debridement and fusion procedure. The surgical time, blood loss, hospital stay, fusion time, and surgical complications were documented. Clinical efficacy was assessed using the visual analogue scale (VAS), the neck disability index (NDI), and the ASIA impairment scale. Preoperative and postoperative data were compared using paired sample t tests, repeated measures analysis of variance, and generalized estimating equations. Results: All the 23 patients underwent the operative procedures successfully. The operation time was (102.8±19.8) minutes (range:60 to 140 minutes), blood loss was (84.4±40.2) ml (range:30 to 160 ml), and the length of hospital stay was (17.4±6.0) days (range:10 to 30 days). Blood cultures were positive for the causative pathogen in 14 cases (60.8% positivity rate), while 9 cases had negative results. Irrigation fluid cultures yielded the causative pathogen in 19 cases (82.6% positivity rate), with 4 cases negative. All patients were followed up for more than 12 months, with a follow-up duration of (19.0±5.9) months (range:12 to 36 months). At the final follow-up, VAS improved from (5.9±1.1) points preoperatively to (0.8±0.3) points; NDI improved from (38.3±6.0)% preoperatively to (9.3±3.0)%, with statistically significant differences (all P<0.01). All patients experienced improvement in neurological function, with the exception of one patient in grade C and two in grade D, all other patients recovered to grade E. The C2-7 Cobb angle and the affected segment Cobb angle were corrected. white blood cell, erythrocyte sedimentation rate and C-reactive protein levels returned to normal. All patients achieved bony fusion, with a fusion time of (8.9±1.9) months (range:6 to 12 months). Two diabetic patients developed postoperative incision infection; no other surgery-related complications occurred in the remaining patients. Conclusion: One-stage anterior debridement and bone graft fusion can correct kyphosis, restore normal alignment, and improve neurological function in the treatment of single and double segment cervical pyogenic spondylodiscitis, representing a viable treatment option for cervical pyogenic spondylodiscitis.

Metabolic disruption impairs ribosomal protein levels, resulting in enhanced aminoglycoside tolerance

Metabolic disruption impairs ribosomal protein levels, resulting in enhanced aminoglycoside tolerance

A case of fulminant cryofibrinogenemia with rapid renal dysfunction and toe necrosis

BackgroundThere are few reports of kidney disease caused by cryofibrinogen (CF). There are still many unknowns regarding its diagnosis, treatment, and prognosis.Case presentationA woman in her 70s experienced gross hematuria without any triggers; no urinary abnormalities had been previously detected. At the same time, the urine protein level was 5 g; therefore, a renal biopsy was performed. Light microscopy revealed a membranoproliferative glomerulonephritis-like pattern. And the electron microscopic findings were extremely characteristic and specific. Development of ischemic lesions was observed in the lower legs. A skin biopsy performed at the sites of toe necrosis showed fibrinoid necrotizing vasculitis and thrombi in the blood vessels. Eventually, the patient was diagnosed with cryofibrinogenemia (CF-emia) by mass spectrometry. The effect of steroids was limited. Subsequently, the patient’s renal function rapidly deteriorated, and toe necrosis progressed. The patient died after initiation of hemodialysis.ConclusionAlthough CF-emia is an unknown disease and has been infrequently reported, no reported cases exhibited rapid worsening of toe necrosis and renal function during the same period. Therefore, this case can be said to be the first case of fulminant cryofibrinogenemia. Due to the development of nephropathy, which is likely to be a factor for poor prognosis, establishment of therapeutic strategies is urgently required.