Gas-propelled nanomotors alleviate colitis through the regulation of intestinal immunoenvironment-hematopexis-microbiota circuits.

The progression of ulcerative colitis (UC) is associated with immunologic derangement, intestinal hemorrhage, and microbiota imbalance. While traditional medications mainly focus on mitigating inflammation, it remains challenging to address multiple symptoms. Here, a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO2 nanospheres with Cu2O nanoblocks. The resulting CaO2-Cu2O possessed a desirable diameter (291.3 nm) and a uniform size distribution. It could be efficiently internalized by colonic epithelial cells and macrophages, scavenge intracellular reactive oxygen/nitrogen species, and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 phenotype. This nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen bubbles. Rectal administration of CaO2-Cu2O could stanch the bleeding, repair the disrupted colonic epithelial layer, and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation, anti-oxidation, wound healing, and anti-inflammation. Impressively, it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria (e.g., Odoribacter and Bifidobacterium) and decreasing the abundances of harmful bacteria (e.g., Prevotellaceae and Helicobacter). Our gas-driven CaO2-Cu2O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

Semaglutide alleviates early brain injury following subarachnoid hemorrhage by suppressing ferroptosis and neuroinflammation via SIRT1 pathway.

OBJECTIVES: Subarachnoid hemorrhage (SAH) is a major cause of incapacity and death, imposing a significant economic burden globally. Additionally, SAH is the third most prevalent form of stroke. Semaglutide affects oxidative stress, inflammation, and mitochondrial biogenesis. Specifically, the potential neuroprotective effect of semaglutide in SAH and its underlying mechanism is unclear. Accordingly, the present research intended to explore the neuroprotective effect of semaglutide in SAH and its potential molecular mechanisms. METHODS: We constructed a C57BL/6 mouse model of SAH. The parameters assessed were neuronal ferroptosis, neuroinflammatory cytokine levels, reactive oxygen species (ROS) levels, glutathione (GSH) and malondialdehyde (MDA) levels, brain water content, and neurological score. RESULTS: The results showed that the activation of semaglutide significantly increased neurological scores, relieved cerebral edema, decreased the levels of inflammatory cytokine nuclear factor kappa B, interleukin (IL)-1ß, IL-6, tumor necrosis factor-alpha, MDA, and ROS, and increased the levels of GSH. Suppression of SIRT1 reversed these effects, indicating that semaglutide activated SIRT1 to reduce neuroinflammation, ferroptosis, and neuronal cell death after SAH. Thus, the activation of the Nrf2/HO-1 signaling pathway contributes to the neuroprotective properties of semaglutide. CONCLUSIONS: Semaglutide can improve murine neurological outcomes and reduce neuronal damage against neuroinflammation and ferroptosis.

Natural lipid nanoparticles extracted from Morus nigra L. leaves for targeted treatment of hepatocellular carcinoma via the oral route.

The clinical application of conventional medications for hepatocellular carcinoma treatment has been severely restricted by their adverse effects and unsatisfactory therapeutic effectiveness. Inspired by the concept of 'medicine food homology', we extracted and purified natural exosome-like lipid nanoparticles (LNPs) from black mulberry (Morus nigra L.) leaves. The obtained MLNPs possessed a desirable hydrodynamic particle size (162.1 nm), a uniform size distribution (polydispersity index = 0.025), and a negative surface charge (-26.6 mv). These natural LNPs were rich in glycolipids, functional proteins, and active small molecules (e.g., rutin and quercetin 3-O-glucoside). In vitro experiments revealed that MLNPs were preferentially internalized by liver tumor cell lines via galactose receptor-mediated endocytosis, increased intracellular oxidative stress, and triggered mitochondrial damage, resulting in suppressing the viability, migration, and invasion of these cells. Importantly, in vivo investigations suggested that oral MLNPs entered into the circulatory system mainly through the jejunum and colon, and they exhibited negligible adverse effects and superior anti-liver tumor outcomes through direct tumor killing and intestinal microbiota modulation. These findings collectively demonstrate the potential of MLNPs as a natural, safe, and robust nanomedicine for oral treatment of hepatocellular carcinoma.

Systemic inflammation and oxidative stress markers in patients with unipolar and bipolar depression: A large-scale study.

OBJECTIVE: Numerous studies have demonstrated that neutrophil/HDL ratio (NHR), lymphocyte/HDL ratio (LHR), monocyte/HDL (MHR) ratio, platelet/HDL ratio (PHR), neutrophil/ALB ratio (NAR) and platelet/ALB ratio (PAR) can serve as systemic inflammation and oxidative stress markers in a variety of diseases. However, few studies have estimated the associations of these markers with unipolar depression (UD) and bipolar depression (BD), as well as psychotic symptoms in UD and BD. METHODS: 6297 UD patients, 1828 BD patients and 7630 healthy subjects were recruited. The differences in these indicators among different groups were compared, and the influencing factors for the occurrence of UD or BD and psychotic symptoms were analyzed. RESULTS: These ratios displayed unique variation patterns across different diagnostic groups. BD group exhibited higher NHR, LHR, MHR, NAR and lower PAR than UD and HC groups, UD group showed higher MHR than HC group. The psychotic UD group had higher NHR, LHR, MHR and NAR than non-psychotic UD group. Higher LHR, MHR, NAR and lower PAR were risk factors in BD when compared to UD group. CONCLUSIONS: Our study demonstrated differences in inflammation and oxidative stress profile between UD and BD patients, as well as between subjects with or without psychotic symptom exist, highlighting the role of inflammation and oxidative stress in the pathophysiology of UD and BD.

Albumin and Associated Biomarkers in Severe Neuropsychiatric Disorders: Acute-Phase Schizophrenia and Bipolar Disorder.

Background: Inflammation is relevant to the pathophysiology of severe neuropsychiatric disorders, schizophrenia (SCZ) and bipolar disorders (BD). Multiple pathophysiological biomarkers are valuable for the study of inflammatory processes. This study investigated albumin-related biomarkers in SCZ and BD to explore their roles in disease. Methods: A total of 5,577 SCZ, 3442 BD-manic (BD-M) and 1405 BD-depression (BD-D) in acute stage and 5000 health controls (HCs) were enrolled. The differences in these biomarker levels among different groups were compared, and the contributing factors for the occurrence of SCZ, BD, and subgroups of BD were analyzed. Results: Both SCZ and BD exhibit lower prognostic nutritional index (PNI), but higher neutrophil percentage-to-albumin ratio (NPAR) and creatinine-albumin ratio (CRA) compared with HC. Compared with BD-D, BD-M had higher NPAR and platelet-to-albumin ratio (PAR) and lower CRA. In logistic regression, lower prognostic nutritional index (PNI) and higher CRA were associated with both SCZ and BD, while higher NPAR was associated with BD. In the subgroup of BD, higher NPAR, CRA and lower PNI were associated with BD-M; lower PAR, PNI and higher CRA were associated with BD-D. Conclusion: Our study reaffirmed the role of inflammation in the pathophysiology of SCZ and BD. Diagnostic value has been demonstrated in NPAR, PAR, PNI and CRA for BD and SCZ.

Mulberry Biomass-Derived Nanomedicines Mitigate Colitis through Improved Inflamed Mucosa Accumulation and Intestinal Microenvironment Modulation.

The therapeutic outcomes of conventional oral medications against ulcerative colitis (UC) are restricted by inefficient drug delivery to the colitis mucosa and weak capacity to modulate the inflammatory microenvironment. Herein, a fluorinated pluronic (FP127) was synthesized and employed to functionalize the surface of mulberry leaf-derived nanoparticles (MLNs) loading with resveratrol nanocrystals (RNs). The obtained FP127@RN-MLNs possessed exosome-like morphologies, desirable particle sizes (around 171.4 nm), and negatively charged surfaces (-14.8 mV). The introduction of FP127 to RN-MLNs greatly improved their stability in the colon and promoted their mucus infiltration and mucosal penetration capacities due to the unique fluorine effect. These MLNs could efficiently be internalized by colon epithelial cells and macrophages, reconstruct disrupted epithelial barriers, alleviate oxidative stress, provoke macrophage polarization to M2 phenotype, and down-regulate inflammatory responses. Importantly, in vivo studies based on chronic and acute UC mouse models demonstrated that oral administration of chitosan/alginate hydrogel-embedding FP127@RN-MLNs achieved substantially improved therapeutic efficacies compared with nonfluorinated MLNs and a first-line UC drug (dexamethasone), as evidenced by decreased colonic and systemic inflammation, integrated colonic tight junctions, and intestinal microbiota balance. This study brings new insights into the facile construction of a natural, versatile nanoplatform for oral treatment of UC without adverse effects.

Recent advances in mucus-penetrating nanomedicines for oral treatment of colonic diseases.

INTRODUCTION: Oral administration is the most common route for treating colonic diseases that present increased incidences in recent years. Colonic mucus is a critical rate-limiting barrier for the accumulation of oral therapeutics in the colonic tissues. To overcome this obstacle, mucus-penetrating nanotherapeutics have been exploited to increase the accumulated amounts of drugs in the diseased sites and improve their treatment outcomes against colonic diseases. AREAS COVERED: In this review, we introduce the structure and composition of colonic mucus as well as its impact on the bioavailability of oral drugs. We also introduce various technologies used in the construction of mucus-penetrating nanomedicines (e.g. surface modification of polymers, physical means and biological strategies) and discuss their mechanisms and potential techniques for improving mucus penetration of nanotherapeutics. EXPERT OPINION: The mucus barrier is often overlooked in oral drug delivery. The weak mucus permeability of conventional medications greatly lowers drug bioavailability. This challenge can be addressed through physical, chemical and biological technologies. In addition to the reported methods, promising approaches may be discovered through interdisciplinary research that further helps enhance the mucus penetration of nanomedicines.

Transdermal delivery of Protocatechuic aldehyde using hyaluronic acid/gelatin-based microneedles for the prevention and treatment of hypertrophic scars.

The formation of hypertrophic scar (HS) involves many pathological processes, such as reduced apoptosis in fibroblasts, excessive collagen deposition by fibroblasts, over-abundant angiogenesis, etc. The therapeutic effects of current treatments targeting one single pathological process are limited. Due to their diverse biological activities, natural products offer a potential solution to this issue. In this study reported herein, we investigated the effects of Protocatechuic aldehyde (PA) on both hypertrophic scar-derived fibroblasts (HSF) and vascular endothelial growth factor (VEGF)-stimulated human umbilical vein endothelial cells (HUVECs). Microneedles (MN) containing PA and hyaluronic acid (HA) or containing PA, HA, and gelatin were prepared by mixing PA stock solution with HA or HA/gelatin at a ratio of 1:10. The HS prevention and treatment outcomes of these HA-PA-MN and HA/gelatin-PA-MN were tested using a rabbit ear HS model. Our data indicate that PA induces apoptosis and reduces collagen deposition in HSF. In addition, PA attenuates VEGF-stimulated angiogenesis of HUVECs. Furthermore, HA-PA-MN or HA/gelatin-PA-MN are able to effectively penetrate the epidermis of the HS tissues and then quickly dissolve, enabling the fast release of PA directly into the dermis of the HS tissues. HA-PA-MN or HA/Gelatin-PA-MN have also been found to effectively prevent or alleviate HS in a rabbit ear HS model. In conclusion, this study demonstrates that PA can be used to prevent and treat HS by simultaneously regulating HSF and HUVECs, which offers a potential novel reagent for HS management.

Effects of ulinastatin therapy in emergency severe multiple trauma: A single-center randomized controlled trial.

BACKGROUND: Severe multiple traumas are one of the most common diseases and carry a significant financial burden with high disability and mortality. There are no effective drugs in the clinical management of severe multiple traumas, and there is an absence of evidence-based medicine concerning the treatment of severe multiple traumas. METHODS: The present study explored whether ulinastatin (UTI) can improve the outcome of severe multiple traumas. The present research included patients who were hospitalized in intensive care units after being diagnosed with severe multiple trauma. Patients received UTIs (400,000 IU) or placebos utilizing computer-based random sequencing (in a 1:1 ratio). The primary outcome measures were 30-day mortality, multiple organ dysfunction syndrome, inflammatory response, coagulation function, infection, liver function, renal function, and drug-related adverse effects. RESULTS: A total of 239 individuals were classified into 2 groups, namely, the placebo group (n = 120) and the UTI group (n = 119). There were no statistically significant differences in baseline clinical data between the 2 groups. The 30-day mortality and multiple organ dysfunction syndrome in the UTI group were remarkably improved compared with those in the placebo group. UTI can protect against hyperinflammation and improve coagulation dysfunction, infection, liver function, and renal function. UTI patients had markedly decreased hospitalization expenditures compared with the placebo group. CONCLUSION: The findings from the present research indicated that UTIs can improve the clinical outcomes of patients with severe multiple traumas and have fewer adverse reactions.

Clarifying sleep characteristics and analyzing risk factors of sleep disorders to promote a predictive, preventive, and personalized medicine in patients with burn scars.

Purpose: This study assessed sleep quality in patients with burn scars and investigated risk factors of sleep disorders to guide clinical therapy. From the strategy of predictive, preventive, and personalized medicine (PPPM/3PM), we proposed that risk assessment based on clinical indicators could prompt primary prediction, targeted prevention, and personalized interventions to improve the management of sleep disorders present in patients with burn scars. Methods: This retrospective study recruited patients with burn scars and healthy volunteers from the Shanghai Burn Treatment Center between 2017 and 2022. Relevant information and data, including demographic characteristics, scar evaluation, and sleep quality, were obtained through the hospital information system, classical scar scale, and self-report questionnaires. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and monitored using a cardiopulmonary-coupled electrocardiograph. Pain and pruritus were assessed using the visual analog scale (VAS). Scar appearance was assessed using the modified Vancouver scar scale (mVSS). Results: The sample was comprised of 128 hypertrophic scar (HS) patients, with 61.7% males, a mean age of 41.1 ± 11.6 years, and burn area of 46.2 ± 27.9% total body surface area (TBSA). Patients with PSQI ≥ 7 accounted for 76.6%, and the global PSQI score was 9.4 ± 4.1. Objective sleep data showed that initial enter deep sleep time, light sleep time, awakening time, light sleep efficiency, and sleep apnea index were higher but deep sleep time, sleep efficiency, and deep sleep efficiency were lower in HS patients than that in healthy controls. Preliminary univariate analysis showed that age, hyperplasia time of scar, narrow airway, microstomia, VAS for pain and pruritus, and mVSS total (comprised of pigmentation, vascularity, height and pliability) were associated with the PSQI score (p < 0.1). Multivariable linear regression showed narrow airway, VAS for pain and pruritus, and mVSS specifically height, were the risk factors for PSQI score (p < 0.1). Conclusions: This study model identified that narrow airway, pain, pruritus and scar appearance specifically height may provide excellent predictors for sleep disorders in HS patients. Our results provided a basis for the predictive diagnostics, targeted prevention, and individualized therapy of somnipathy predisposition and progression of HS patients in the setting of PPPM/3PM health care system, which contributed to a paradigm shift from reactive cure to advanced therapy.

Recent advances in natural polysaccharides-based controlled release nanosystems for anti-cancer phototherapy.

Phototherapy, which relies on light to trigger phototherapeutic agents (PAs) to generate cytotoxic reactive oxygen species or hyperthermia, has received much attention in cancer treatment. However, traditional PAs have shortcomings such as low water solubility, easy aggregation-induced fluorescence quenching and low target site accumulation efficiency, which severely limit clinical anticancer applications. Naturally derived polysaccharides have attracted great attention in the scientific community in nano-drug delivery systems (NDDS) due to their abundant resources, biocompatibility, targeting ability, bioactivity and so on, which is expected to assist PAs to play a synergistic effect. This article reviews the recent progress of polysaccharides in the field of cancer phototherapy, including the advantages of polysaccharides as nanocarrier materials to deliver PAs; the main mechanism for the preparation of PAs-loaded polysaccharides nanoformulation; construction of polysaccharides-based NDDS for delivery of PAs and its functional modification strategy, hoping to further improve the therapeutic effect of phototherapy against cancer.

Non-enzymatic antioxidants, macro-minerals and monocyte/high-density lipoprotein cholesterol ratio among patients with bipolar disorder.

OBJECTIVE: Recent studies show that oxidative stress is related to the pathogenesis of BD. Non-enzymatic antioxidants, macro-minerals and MHR (monocyte divided by high-density lipoprotein cholesterol) participated oxidative stress and can be obtained quickly in hematological examination. This study used large-scale clinical data to investigate them between BD and healthy controls (HCs), as well as between psychotic and non-psychotic BD to explore their roles in disease progression. METHODS: A total of 3442 BD-manic (BD-M) and 1405 BD-depression (BD-D) in acute stage and 5000 HCs were enrolled, including 1592 BD-M with psychotic symptoms (P-BD-M), 1850 BD-M without psychotic symptoms (NP-BD-M), 655 P-BD-D, 750 NP-BD-D. The differences in these biological parameter levels among different groups were compared, and the contributing factors for the occurrence of BD-M or BD-D and psychotic symptoms of BD were analyzed. RESULTS: We found higher levels of Na and MHR, and lower levels of K, Ca and ALB in BD-M or BD-D compared with the HCs respectively; levels of K, Na, Ca, ALB and MHR have differences among P-BD-M, NP-BD-M and HC; levels of K, Na, Ca and ALB have differences among P-BD-D, NP-BD-D and HC. In multiple logistic regression, higher levels of MHR and Na were associated with BD-M; MHR was shown to be independently associated with P-BD-M; K, Na, ALB were shown to be independently associated with P-BD-D. CONCLUSIONS: Our study highlights the role of oxidative stress in the pathophysiology of BD. There is heterogeneity between BD-M and BD-D, and different oxidative stress mechanisms of psychotic symptoms exist in BD-M and BD-D.

Performance of the IMPACT and Helsinki models for predicting 6-month outcomes in a cohort of patients with traumatic brain injury undergoing cranial surgery.

Background and aim: Prediction models for patients with traumatic brain injury (TBI) require generalizability and should apply to different settings. We aimed to validate the IMPACT and Helsinki prognostic models in patients with TBI who underwent cranial surgery in a Chinese center. Methods: This validation study included 607 surgical patients with moderate to severe TBI (Glasgow Coma Scale [GCS] score ≤12) who were consecutively admitted to the Neurotrauma Center of People's Liberation Army (PLANC), China, between 2009 and 2021. The IMPACT models (core, extended and lab) and the Helsinki CT clinical model were used to estimate 6-month mortality and unfavorable outcomes. To assess performance, we studied discrimination and calibration. Results: In the PLANC database, the observed 6-month mortality rate was 28%, and the 6-month unfavorable outcome was 52%. Significant differences in case mix existed between the PLANC cohort and the development populations for the IMPACT and, to a lesser extent, for the Helsinki models. Discrimination of the IMPACT and Helsinki models was excellent, with most AUC values ≥0.80. The highest values were found for the IMPACT lab model (AUC 0.87) and the Helsinki CT clinical model (AUC 0.86) for the prediction of unfavorable outcomes. Overestimation was found for all models, but the degree of miscalibration was lower in the Helsinki CT clinical model. Conclusion: In our population of surgical TBI patients, the IMPACT and Helsinki CT clinical models demonstrated good performance, with excellent discrimination but suboptimal calibration. The good discrimination confirms the validity of the predictors, but the poorer calibration suggests a need to recalibrate the models to specific settings.

Ablative fractional carbon dioxide laser improves quality of life in patients with extensive burn scars: A nested case-control study.

BACKGROUND AND OBJECTIVES: Ablative fractional carbon dioxide laser (CO2 -AFL) for small-area burn scar management shows encouraging outcomes. Few studies, however, focused on comprehensive outcomes following CO2 -AFL treatment for extensive burn scars. This study evaluated whether CO2 -AFL surgery improved the quality of life (QoL) for burn survivors with extensive hypertrophic scars. METHODS: A retrospective nested case-control study was initiated to analyze the efficacy of CO2 -AFL treatment for patients with large-area burn scars. Patients with extensive burn scars (≥30% total body surface area [TBSA]) were registered in our hospital from March 2016 to October 2018. Patients undergoing CO2 -AFL surgery were divided into CO2 -AFL group, and patients undergoing conventional surgery were matched in a 1:1 ratio as the conventional surgery group according to the burned area. The questionnaires were collected and followed up. The 36-Item Short Form Health Survey (SF-36) and Burns Specific Health Scale-Brief (BSHS-B) were the primary parameters. Secondary parameters included the Pittsburgh Sleep Quality Index (PSQI), University of North Carolina "4P" Scars Scale (UNC4P), Patient Scars Assessment Scale for Patient (POSAS-P), and Douleur Neuropathique 4 questions (DN4). RESULTS: 23 patients (55.96 ± 21.59% TBSA) were included in CO2 -AFL group and 23 patients (57.87 ± 18.21% TBSA) in conventional surgery group. Both the BSHS-B total score (CO2 -AFL vs. conventional surgery: 115.35 ± 29.24 vs. 85.43 ± 33.19, p = 0.002) and the SF-36 total score (CO2 -AFL vs. conventional surgery: 427.79 ± 118.27 vs. 265.65 ± 81.66, p < 0.001) for the CO2 -AFL group were higher than those for the conventional surgery group. Parameters for the CO2 -AFL group were lower than those for the conventional surgery group in all of the following comparisons: PSQI total score (CO2 -AFL vs. conventional surgery: 7.70 ± 3.74 vs. 12.26 ± 4.61, p = 0.001), POSAS-P total score (CO2 -AFL vs. conventional surgery: 26.48 ± 6.60 vs. 33.04 ± 4.56, p < 0.001), UNC4P total score (CO2 -AFL vs. conventional surgery: 5.57 ± 1.97 vs. 7.26 ± 1.81, p = 0.004), and DN4 score (CO2 -AFL vs. conventional surgery: 3 [2-5] vs. 5 [4-8], p = 0.004). CONCLUSIONS: Compared to conventional surgery, whole scar CO2 -AFL surgery dramatically improved physical and mental health as well as QoL for people with extensive burn scars. Additionally, CO2 -AFL enhanced the evaluation of scars including their appearance, pain, itching, and a host of other symptoms.

Investigation of systemic immune-inflammation index, neutrophil/high-density lipoprotein ratio, lymphocyte/high-density lipoprotein ratio, and monocyte/high-density lipoprotein ratio as indicators of inflammation in patients with schizophrenia and bipolar disorder.

Background: The systemic immune-inflammation index (SII), system inflammation response index (SIRI), neutrophil/high-density lipoprotein (HDL) ratio (NHR), lymphocyte/HDL ratio (LHR), monocyte/HDL ratio (MHR), and platelet/HDL ratio (PHR) have been recently investigated as new markers for inflammation. The purpose of this research is to use large-scale clinical data to discuss and compare the predictive ability of the SII, SIRI, NHR, LHR, MHR, and PHR in patients with schizophrenia (SCZ) and bipolar disorder (BD), to investigate potential biomarkers. Materials and methods: In this retrospective, naturalistic, cross-sectional study, we collected the hematological parameter data of 13,329 patients with SCZ, 4,061 patients with BD manic episodes (BD-M), and 1,944 patients with BD depressive episodes (BD-D), and 5,810 healthy subjects served as the healthy control (HC) group. The differences in the SII, SIRI, NHR, LHR, MHR, and PHR were analyzed, and a receiver operating characteristic (ROC) curve was used to analyze the diagnostic potential of these parameters. Results: Compared with the HC group, the values of the SII, SIRI, NHR, LHR, MHR, and PHR and the levels of neutrophils, monocytes, and triglycerides (TG) were higher in SCZ and BD groups, and levels of platelets, cholesterol (CHO), HDL, low-density lipoprotein (LDL), and apoprotein B (Apo B) were lower in SCZ and BD groups. Compared to the BD group, the values of the SIRI, lymphocytes, monocytes, and HDL were lower and the values of the SII, NHR, PHR, and platelet were higher in the SCZ group. In contrast to the BD-D group, the values of the SII; SIRI; NHR; and MHR; and levels of neutrophils, monocytes, and platelets were higher in the BD-M group, and the levels of CHO, TG, LDL, and Apo B were lower in the BD-M group. The MHR and NHR were predictors for differentiating the SCZ group from the HC group; the SIRI, NHR, and MHR were predictors for differentiating the BD-M group from the HC group; and the MHR was a predictor for differentiating the BD-D group from the HC group. The combination model of the indicators improved diagnostic effectiveness. Conclusion: Our study highlights the role of systemic inflammation in the pathophysiology of SCZ, BD-M, and BD-D, the association between inflammation and lipid metabolism, and these inflammation and lipid metabolism indicators showed different variation patterns in SCZ, BD-D, and BD-M.

Combination of chemically modified SDF-1α mRNA and small skin improves wound healing in diabetic rats with full-thickness skin defects.

OBJECTIVES: Diabetes mellitus is associated with refractory wound healing, yet current therapies are insufficient to accelerate the process of healing. Recent studies have indicated chemically modified mRNA (modRNA) as a promising therapeutic intervention. The present study aimed to explore the efficacy of small skin engineered to express modified mRNAs encoding the stromal cell-derived factor-1α (SDF-1α) facilitating wound healing in a full-thickness skin defect rat model. This study, devised therapeutic strategies for diabetic wounds by pre-treating small skin with SDF-1α modRNA. MATERIALS AND METHODS: The in vitro transfection efficiency was evaluated using fluorescence microscopy and the content of SDF-1α in the medium was determined using ELISA after the transfection of SDF-1α into the small skin. To evaluate the effect of SDF-1α modRNA and transplantation of the small skin cells on wound healing, an in vivo full-thickness skin defect rat model was assessed. RESULTS: The results revealed that a modRNA carrying SDF-1α provided potent wound healing in the small skin lesions reducing reduced scar thickness and greater angiogenesis (CD31) in the subcutaneous layer. The SDF-1α cytokines were significantly secreted by the small skin after transfection in vitro. CONCLUSIONS: This study demonstrated the benefits of employing small skin combined with SDF-1α modRNA in enhancing wound healing in diabetic rats having full-thickness skin defects.

BIRC7 is Beneficial for Melanoma Progression and Hypoxic Response.

Background: Cutaneous melanoma (CM) accounts for about 90% of all melanoma cases. HIF-1α overexpression is associated with poor prognosis in many cancers including CM. Hence, we characterized differentially expressed genes (DEGs) in the response of CM cells to normoxia and hypoxia. Methods: We first successfully constructed cell hypoxia model and then performed RNA-seq to explore the changes of gene transcription in CM cells during hypoxia. The highest expression of the six genes was detected using qRT-PCR and Western blot assays. The binding sites between BIRC7 promoter and HIF-1α was explored by luciferase assay. Cellular function assays were used to observe the role of BIRC7 in the effect of hypoxia on tumor progression. Results: Compared with the transcriptome data of the control group, a total of 2601 DEGs were identified in the hypoxic group. There were 1517 genes with significantly higher expression and 1084 genes with lower expression in the hypoxic group. Among them, OSCAR, BIRC7, HBA1, SFN, GOLT1A, and BEX2 were significantly up-regulated in the hypoxic group. BIRC7 expression was most significantly up-regulated and a downstream factor of HIF-1α. We highlighted that knockdown of BIRC7 reversed the positive effects of HIF-1α on A875 and M14 cells. Conclusion: Our findings demonstrated that BIRC7 was a downstream factor of HIF-1α and reversed the effect of hypoxia on promoting tumor progression of CM cells.

Relation Between Unconjugated Bilirubin and Peripheral Biomarkers of Inflammation Derived From Complete Blood Counts in Patients With Acute Stage of Schizophrenia.

Background: Inflammation and oxidative stress are the major leading hypothetical causes of schizophrenia. Unconjugated bilirubin (UCB) is an efficient endogenous plasma antioxidant. Inflammation is closely linked to oxidative stress. The relationship between UCB and inflammatory markers should be paid close attention in schizophrenia acute stage. In this paper, combined UCB and inflammatory markers were evaluated for their capability in predicting schizophrenia in the acute stage to find an easy and effective indicator to identify acute schizophrenia. Methods: A total of 6,937 acute schizophrenia patients and 6,404 healthy controls (HCs) were enrolled. UCB and peripheral biomarkers of inflammation derived from complete blood counts (CBC) were investigated in the subjects with acute schizophrenia, and the results were compared with HCs. Simultaneously, Spearman test was employed to assess the correlation between the variables, while logistic regression was adopted to determine the combined equation and receiver operating characteristic curve was used to evaluate the combined value of UCB and peripheral biomarkers of inflammation derived from CBC to predict schizophrenia in the acute stage. Results: The study indicates that white blood cells, neutrophil, monocyte, mean platelet volume (MPV), red cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), and monocyte/lymphocyte ratio (MLR) have significantly increased in schizophrenia (p < 0.05 for all), while platelet, lymphocyte, and platelet/lymphocyte ratio (PLR) in schizophrenia have significantly decreased (p < 0.05 for all). UCB exhibits negative correlation with MPV significantly (r = 0.121, p < 0.001), and no correlation with neutrophil and monocyte. The correlations between UCB and other peripheral biomarkers of inflammation derived from CBC are very weak. MPV, RDW, NLR, MLR, PLR, and UCB were taken as independent variables for a logistic regression analysis. The model was as follows: Logit  ( P 1 ) = - 6 . 141 + 0 . 827  MPV + 5 . 613  MLR - 0 . 005  PLR - 0 . 346  UBC . The combination demonstrates better effectiveness in predicting schizophrenia in the acute stage (AUC 0.831, 95% CI 0.825 to 0.837). Conclusion: UCB has a protective effect on acute stage of schizophrenia, which is weak and indirect by affecting the proinflammatory processes. Our findings suggest that a combination of MLR, MPV, PLR, and UBC could be used to predict acute stage of schizophrenia.

Skin Wound Tension Reduction Device Combined with Ablative Fractional Carbon Dioxide Laser to Reduce Scar Formation After Excision of Pediatric Facial Skin Lesions: A Prospective Cohort Study.

PURPOSE: To investigate the efficacy of skin wound tension reduction device (SWTRD) combined with ablative fractional carbon dioxide laser (CO2-AFL) for the prevention of scar formation following the excision of facial cutaneous lesions in children. METHODS: Patients undergoing surgical excision of facial cutaneous lesions in our hospital between May 2019 and April 2021 were enrolled. After the excision of facial cutaneous lesions and based on the personal intents and conditions, patients were assigned to undergo SWTRD combined with CO2-AFL. Outcome evaluations were as follows: defect size, incision width, scar width, the Vancouver Scar Scale (VSS) and University of North Carolina 4P Scar Scale (UNC4P). RESULTS: A total of 25 pediatric patients (mean age, 9.88 years) were enrolled in the study. Following the treatment of SWTRD+CO2-AFL, scar widths were relatively narrow and the appearance of the incision scars was significantly improved. A significant reduction in the patient-reported UNC4P scores at 6 months (3, 1-4) was observed when compared with that at 2 months (0, 0-1) after surgery (p<0.001). A similar reduction in the VSS scar scale was also evident (6 months: 1, 0.75-2.5 vs 2 months: 6.5-8.5; p<0.001). CONCLUSION: Combined SWTRD and CO2-AFL treatment effectively modulates the scar formation after the incision is healed and resulting in preventing scar widening, leading to the improvement of scar appearance, reduction in wound pain and pruritus and its overall prognosis.

Anti-inflammatory effect of Rhein on ulcerative colitis via inhibiting PI3K/Akt/mTOR signaling pathway and regulating gut microbiota.

This study aimed to analyze the therapeutic effect of Rhein on ulcerative colitis (UC) in mice and its possible mechanism. LPS-induced UC cell model and DSS-induced UC mouse model were used to analyze the antiinflammatory effect of Rhein on UC in vitro and in vivo, respectively. Network pharmacology analysis was conducted to identify potential signaling pathways involved in Rhein treating UC, and the results were further confirmed through western blotting assay. 16sRNA sequencing was performed to study the regulatory effect of Rhein on gut microbiota in UC mice. As indicated by the results, Rhein could significantly inhibit the production of pro-inflammatory cytokines (e.g., TNF-α, IL-6 and IL-1ß) in vivo and in vitro, and alleviate DSS-induced UC-associated symptoms in mice (e.g., colon shortening, weight loss, diarrhea and hematochezia). The PI3K/Akt/mTOR signaling pathway was predicted as the potential interacting protein of Rhein in the treatment of UC through network pharmacology analysis. It was found through western blotting assay that the Rhein treatment could significantly inhibit the PI3K/Akt/mTOR signaling pathway by decreasing the phosphorylated protein levels of PI3K, Akt, mTOR and p70S6K1. By 16sRNA gene sequencing analysis, Rhein administration could partially reverse the gut dysbacteriosis of mice induced by DSS and decrease pathogenic bacteria (e.g., Enterobacteriaceae and Turicibacter). It was positively correlated with the production of pro-inflammatory cytokines above, whereas the increase in probiotics (e.g., Unspecified-S24-7 and Rikenellaceae) was negatively correlated with the production of pro-inflammatory cytokines. In conclusion, Rhine had anti-UC efficacy, which was demonstrated by mitigating the UC symptoms and reducing intestinal inflammation by inhibiting the PI3K/Akt/mTOR signaling pathway and modulating gut microbiota.