Mobility Group Research Articles

Examining the effectiveness of knowledge governance mechanisms in mobile messaging groups within construction project teams

PurposeMobile messaging groups (MMGs) have been widely adopted in construction practice, yet, little is known about how to foster knowledge sharing (KS) in MMGs, characterized by communication visibility. This study is thus motivated to investigate mechanisms for KS in this context.Design/methodology/approachThe paper employs knowledge governance theory to construct a theoretical model and develop hypotheses. Specifically, psychological safety is identified as a mediator between knowledge governance mechanism (KGM) and KS, and promotion regulatory focus is identified as a moderator between KGM and psychological safety. Data from 208 Chinese construction project team members are collected to test the proposed theoretical model.FindingsThe results suggest that both formal and informal KGM positively affect psychological safety, which in turn improves KS (quantity and quality). Moreover, the mediating role of psychological safety is confirmed, and the moderating role of promotion regulatory focus is validated.Originality/valueThis study explores how to foster KS in MMGs, which are pervasive in today’s digital age. The findings in this study enhance the understanding of KS in digital environments and afford important insights into knowledge management within construction project teams.

Determinants of social participation in people with disability.

In this study, it is aimed to determine personal wellbeing and social participation levels across different physical disability types and levels of mobility. A sample of 85 individuals with physical disabilities, excluding those with mental disabilities were included. Sociodemographics, mobility of the participants, cause, duration of disability were recorded. Personal Wellbeing Index-Adult (PWI-A) scale was used for the assessment of wellbeing and Keele Assessment of Participation (KAP) for social participation. Female, single, unemployed subjects and individuals with neurologic disability showed significantly higher median KAP-scores(p = 0.009, p = 0.050, p<0.001, p = 0.050, respectively).The median KAP-score of the independently mobile group was significantly lower compared to the other two groups (p = 0.001). The factors affecting KAP were determined as employment, mobility level and personal wellbeing (p = 0.002, p = 0.024, p = 0.050, respectively). Mobility level, employment and personal wellbeing are the determinants of social participation in people with disabilities. Neurological disability, female gender, being single, unemployment and mobility limitations are factors that reduce social participation.

Mobilization with Femoral Catheters in the Burn ICU: A retrospective review following change in practice guidelines.

Femoral catheters are a known barrier for Burn ICU mobility progression due to the anatomical location and potential risk of complications. The purpose of this study was to examine outcomes and complication rates following implementation of femoral catheter mobilization guidelines, as well as determine safety and feasibility of mobilization with femoral catheters in place within the burn population. Retrospective review was completed on 17 patients prior to and following implementation of new femoral catheter mobility guidelines, 34 patients total. Burn therapy notes were reviewed for burn admissions with at least one femoral catheter in place, including arterial, central, and dialysis catheters. Demographic data, admission statistics, line placement timelines, and active mobility achieved during therapy sessions were recorded for both the non-mobilization (NMG) and mobilization groups (MG). The 34 patients reviewed had 99 total lines placed (30 NMG, 69 MG). Change in mobility protocols for the MG resulted in more therapy sessions (n=516 vs 281) and a significant increase in active mobility sessions (n=83 vs 5, p < 0.001), including 146 total mobility activities such as transitions to chairs, tilt table, sitting edge of bed (EOB), standing, active chair transfers, ambulation, and cycle ergometry. No catheter associated adverse events occurred during active mobility sessions and no complications were associated with participation in mobility. This study supports that the presence of femoral catheters alone should not limit the progression of mobility interventions. Using clinical judgement and specialty training, burn therapists can safely mobilize burn ICU patients with femoral catheters in place.

Home exercise is considered essential, but patient compliance remains a mystery

BackgroundRegular exercise is essential in the treatment of Ankylosing Spondylitis (AS), as the main goals of the treatment are to reduce pain, restore function, avoid disability and structural deterioration, and improve quality of life (QoL). The purpose of this study is to ascertain whether patients adhere to exercise recommendations and to evaluate the effects of consistent exercise on patients' pain, function, disease activity, mood, and quality of life. Many studies emphasize the need for exercise in treatment of AS, but none reveal whether patients follow prescribed practices and the results of doing so.ResultsExercising group had significantly decreased pain, erythrocyte sedimentation rate and Bath ankylosing spondylitis functional index and Bath ankylosing spondylitis disease activity index (BASDAI) scores (p < 0.05). There was no significant difference between the two groups in morning stiffness, mood, spinal mobility, and QoL parameters (p > 0.05). Regular exercise was positively correlated with physiotherapy history. Regression analysis revealed that with an increase of 1 unit in visual analog scale and BASDAI, regular exercise decreased by 0.087 and 0.116 units, respectively.ConclusionOur study revealed how much the patients considers and follows the recommended exercises and concluded that regular exercise habits should be developed since they offer promising effects in treatment of AS, hence, patients should be educated in this area, and particular exercise routines should be developed to encourage them to exercise.

Biomechanical Integrity Score of the Female Pelvic Floor for Stress Urinary Incontinence.

This study is aimed at developing and validating a new integral parameter, the Biomechanical Integrity score (BI-score) of the female pelvic floor for stress urinary incontinence conditions. A total of 130 subjects were included in the observational cohort study; 70 subjects had normal pelvic floor conditions, and 60 subjects had stress urinary incontinence (SUI). A Vaginal Tactile Imager (VTI) was used to acquire and automatically calculate 52 biomechanical parameters for eight VTI test procedures (probe insertion, elevation, rotation, Valsalva maneuver, voluntary muscle contractions in two planes, relaxation, and reflex contraction). Statistical methods were applied (t test, correlation) to identify the VTI parameters sensitive to the pelvic SUI conditions. Twenty-seven parameters were identified as statistically sensitive to SUI development. They were subdivided into five groups to characterize tissue elasticity (group 1), pelvic support (group 2), pelvic muscle contraction (group 3), involuntary muscle relaxation (group 4), and pelvic muscle mobility (group 5). Every parameter was transformed to its standard deviation units using the dataset for normal pelvic conditions, similar to the T-score for bone density. Linear combinations with specified weights led to the composition of five component parameters for groups 1-5 and to the BI-score in standard deviation units. The p value for the BI-score has p = 4.0 × 10-28 for SUI versus normal conditions. Quantitative transformations of the pelvic tissues, support structures, and functions under diseased conditions may be studied with the SUI BI-score in future research and clinical applications.

MSC-derived exosomal miR-140-3p improves cognitive dysfunction in sepsis-associated encephalopathy by HMGB1 and S-lactoylglutathione metabolism

MiRNAs in mesenchymal stem cells (MSCs)-derived exosome (MSCs-exo) play an important role in the treatment of sepsis. We explored the mechanism through which MSCs-exo influences cognitive impairment in sepsis-associated encephalopathy (SAE). Here, we show that miR-140-3p targeted Hmgb1. MSCs-exo plus miR-140-3p mimic (Exo) and antibiotic imipenem/cilastatin (ABX) improve survival, weight, and cognitive impairment in cecal ligation and puncture (CLP) mice. Exo and ABX inhibit high mobility group box 1 (HMGB1), IBA-1, interleukin (IL)-1β, IL-6, iNOS, TNF-α, p65/p-p65, NLRP3, Caspase 1, and GSDMD-N levels. In addition, Exo upregulates S-lactoylglutathione levels in the hippocampus of CLP mice. Our data further demonstrates that Exo and S-lactoylglutathione increase GSH levels in LPS-induced HMC3 cells and decrease LD and GLO2 levels, inhibiting inflammatory responses and pyroptosis. These findings suggest that MSCs-exo-mediated delivery of miR-140-3p ameliorates cognitive impairment in mice with SAE by HMGB1 and S-lactoylglutathione metabolism, providing potential therapeutic targets for the clinical treatment of SAE.

HMGN1 loss sensitizes lung cancer cells to chemotherapy

The high mobility group nucleosome binding (HMGN) family, constitutes a large family of non-histone protein family known to bind the acidic patch of the nucleosomes with various key cellular functions. Several studies have highlighted the pivotal roles of HMGNs in the pathogenic process of various cancer types. However, the roles of HMGN family in lung adenocarcinoma (LUAD) have not been fully elucidated. Herein, integrative analyses of multiple-omics data revealed that HMGNs frequently exhibit dysregulation in LUAD. Subsequent analysis of the clinical relevance of HMGN1 demonstrated its association with poor prognosis in LUAD and its potential as a diagnostic marker to differentiate LUAD from healthy controls. Additionally, functional enrichment analysis suggested that HMGN1 was mainly involved in DNA repair. To corroborate these findings, cellular experiments were conducted, confirming HMGN1’s crucial involvement in homologous recombination repair and its potential to enhance the sensitivity of LUAD cells to standard chemotherapeutic drugs. This study proposes HMGN1 as a novel prognostic biomarker and a promising target for chemotherapy in lung adenocarcinoma.

Antileukemic potential of methylated indolequinone MAC681 through immunogenic necroptosis and PARP1 degradation

BackgroundDespite advancements in chronic myeloid leukemia (CML) therapy with tyrosine kinase inhibitors (TKIs), resistance and intolerance remain significant challenges. Leukemia stem cells (LSCs) and TKI-resistant cells rely on altered mitochondrial metabolism and oxidative phosphorylation. Targeting rewired energy metabolism and inducing non-apoptotic cell death, along with the release of damage-associated molecular patterns (DAMPs), can enhance therapeutic strategies and immunogenic therapies against CML and prevent the emergence of TKI-resistant cells and LSC persistence.MethodsTranscriptomic analysis was conducted using datasets of CML patients' stem cells and healthy cells. DNA damage was evaluated by fluorescent microscopy and flow cytometry. Cell death was assessed by trypan blue exclusion test, fluorescent microscopy, flow cytometry, colony formation assay, and in vivo Zebrafish xenografts. Energy metabolism was determined by measuring NAD+ and NADH levels, ATP production rate by Seahorse analyzer, and intracellular ATP content. Mitochondrial fitness was estimated by measurements of mitochondrial membrane potential, ROS, and calcium accumulation by flow cytometry, and morphology was visualized by TEM. Bioinformatic analysis, real-time qPCR, western blotting, chemical reaction prediction, and molecular docking were utilized to identify the drug target. The immunogenic potential was assessed by high mobility group box (HMGB)1 ELISA assay, luciferase-based extracellular ATP assay, ectopic calreticulin expression by flow cytometry, and validated by phagocytosis assay, and in vivo vaccination assay using syngeneic C57BL/6 mice.ResultsTranscriptomic analysis identified metabolic alterations and DNA repair deficiency signatures in CML patients. CML patients exhibited enrichment in immune system, DNA repair, and metabolic pathways. The gene signature associated with BRCA mutated tumors was enriched in CML datasets, suggesting a deficiency in double-strand break repair pathways. Additionally, poly(ADP-ribose) polymerase (PARP)1 was significantly upregulated in CML patients’ stem cells compared to healthy counterparts. Consistent with the CML patient DNA repair signature, treatment with the methylated indolequinone MAC681 induced DNA damage, mitochondrial dysfunction, calcium homeostasis disruption, metabolic catastrophe, and necroptotic-like cell death. In parallel, MAC681 led to PARP1 degradation that was prevented by 3-aminobenzamide. MAC681-treated myeloid leukemia cells released DAMPs and demonstrated the potential to generate an immunogenic vaccine in C57BL/6 mice. MAC681 and asciminib exhibited synergistic effects in killing both imatinib-sensitive and -resistant CML, opening new therapeutic opportunities.ConclusionsOverall, increasing the tumor mutational burden by PARP1 degradation and mitochondrial deregulation makes CML suitable for immunotherapy.

Remote ischemic preconditioning versus sham-control for prevention of anastomotic leakage after resection for rectal cancer (RIPAL trial): a pilot randomized controlled, triple-blinded monocenter trial

PurposeRemote ischemic preconditioning (RIPC) reportedly reduces ischemia‒reperfusion injury (IRI) in various organ systems. In addition to tension and technical factors, ischemia is a common cause of anastomotic leakage (AL) after rectal resection. The aim of this pilot study was to investigate the potentially protective effect of RIPC on anastomotic healing and to determine the effect size to facilitate the development of a subsequent confirmatory trial.Materials and methodsFifty-four patients with rectal cancer (RC) who underwent anterior resection were enrolled in this prospectively registered (DRKS0001894) pilot randomized controlled triple-blinded monocenter trial at the Department of Surgery, University Medicine Mannheim, Mannheim, Germany, between 10/12/2019 and 19/06/2022. The primary endpoint was AL within 30 days after surgery. The secondary endpoints were perioperative morbidity and mortality, reintervention, hospital stay, readmission and biomarkers of ischemia‒reperfusion injury (vascular endothelial growth factor, VEGF) and cell death (high mobility group box 1 protein, HMGB1). RIPC was induced through three 10-min cycles of alternating ischemia and reperfusion to the upper extremity.ResultsOf the 207 patients assessed, 153 were excluded, leaving 54 patients to be randomized to the RIPC or the sham-RIPC arm (27 each per arm). The mean age was 61 years, and the majority of patients were male (37:17 (68.5:31.5%)). Most of the patients underwent surgery after neoadjuvant therapy (29/54 (53.7%)) for adenocarcinoma (52/54 (96.3%)). The primary endpoint, AL, occurred almost equally frequently in both arms (RIPC arm: 4/25 (16%), sham arm: 4/26 (15.4%), p = 1.000). The secondary outcomes were comparable except for a greater rate of reintervention in the sham arm (9 (6–12) vs. 3 (1–5), p = 0.034). The median duration of endoscopic vacuum therapy was shorter in the RIPC arm (10.5 (10–11) vs. 38 (24–39) days, p = 0.083), although the difference was not statistically significant.ConclusionA clinically relevant protective effect of RIPC on anastomotic healing after rectal resection cannot be assumed on the basis of these data.

The mechanism of high mobility group box-1 protein and its bidirectional regulation in tumors.

High-mobility group box-1 protein (HMGB1) is a nonhistone chromatin-related protein widely found in eukaryotic cells. It is involved in the transcription, replication, and repair of DNA to maintain nuclear homeostasis. It participates in cell growth, differentiation, and signal transduction. Recent studies showed that HMGB1 has a bidirectional regulatory effect on tumors by regulating TLR4/MYD88/NF-κB and RAGE/AMPK/mTOR signaling pathways. On the one hand, it is highly expressed in a variety of tumors, promoting tumor proliferation and invasion, while on the other hand, it induces autophagy and apoptosis of tumor cells and stimulates tumor-infiltrating lymphocytes to produce an anti-tumor immune response. At present, HMGB1 could be used as a target to regulate the drug resistance and prognostication in cancer. Clinical applications of HMGB1 in cancer need further in-depth studies.

Design, synthesis, and antitumor mechanism investigation of iridium(III) complexes conjugated with ibuprofen

The design and synthesis of a series of metal complexes formed by non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen (IBP) and iridium(III), with the molecular formula [Ir(C^N)2bpy(4-CH2OIBP-4’-CH2OIBP)](PF6) (Ir-IBP-1, Ir-IBP-2) (C^N = 2-phenylpyridine (ppy, Ir-IBP-1), 2-(2-thienyl)pyridine (thpy, Ir-IBP-2)) was introduced in this article. Firstly, it was found that the anti-proliferative activity of these complexes was more effective than that of cisplatin. Further research showed that Ir-IBP-1 and Ir-IBP-2 can accumulate in intracellular mitochondria, thereby disrupting mitochondrial membrane potential (MMP), increasing intracellular reactive oxygen species (ROS), blocking the G2/M phase of the cell cycle, and inducing cell apoptosis. In terms of protein expression, the expression of COX-2, MMP-9, NLRP3 and Caspase-1 proteins can be downregulated, indicating their ability to anti-inflammatory and overcome immune evasion. Furthermore, Ir-IBP-1 and Ir-IBP-2 can induce immunogenic cell death (ICD) by triggering the release of cell surface calreticulin (CRT), high mobility group box 1 (HMGB1) and adenosine triphosphate (ATP). Overall, iridium(III)-IBP conjugates exhibit various anti-tumor mechanisms, including mitochondrial damage, cell cycle arrest, inflammatory suppression, and induction of ICD.

GET-UP Trial 1-year results: long-term impact of an early mobilization protocol on functional performance after surgery for chronic subdural hematoma.

Evidence on timing for mobilization after chronic subdural hematoma (cSDH) surgery is heterogeneous, and practices differ considerably among neurosurgical centers. The Impact of an Early Out-of-Bed Paradigm in Postoperative Outcomes of Chronic Subdural Hematomas: GET-UP Randomized Prospective Trial (GET-UP Trial) is a randomized clinical trial comparing a postoperative early mobilization protocol to bed rest. Previously reported results at clinical discharge and 1 month after surgery indicated a decreased risk of medical complications in the early mobilization group. Herein, the authors report outcomes at the 1-year follow-up. The GET-UP Trial is a prospective, randomized, unicentric, open-label study with an intention-to-treat primary analysis designed to evaluate the impact of an early mobilization protocol after burr hole craniostomy for cSDH on the occurrence of medical complications and functional outcomes. Between January 2019 and August 2021, a total of 208 patients were recruited and randomized to either an early mobilization group, in which patients began elevation of the head of the bed within the first 12 hours after surgery, or to a bed rest group, in which patients remained recumbent for 48 hours. Outcomes assessed at the 1-year follow-up included functional status as measured by the Glasgow Outcome Scale-Extended (GOSE) and repeat surgery for hematoma recurrence (surgical recurrence). A total of 203 patients completed 1 year of follow-up: 101 in the bed rest group and 102 in the early mobilization group. No significant baseline pre-randomization clinical differences were observed between the two management groups. At 1 year after surgery, a favorable functional outcome, defined as a GOSE score ≥ 5, was observed in 59 patients (58.4%) in the bed rest group and 78 (76.5%) in the early mobilization group (p = 0.006). Death occurred in 25 patients (24.8%) in the bed rest group and 16 (15.7%) in the early mobilization group (p = 0.108). Surgical recurrence was noted in 6 patients (5.9%) in the bed rest group and 7 (6.9%) in the early mobilization group (p = 0.788). Multivariate analysis showed an independent association between early mobilization and an increase in favorable functional outcomes (OR 2.006, 95% CI 1.076-3.739, p = 0.028). The GET-UP Trial is the first randomized clinical trial assessing the impact of mobilization strategies on medical complications after burr hole craniostomy for cSDH. Regarding functional results 1 year after surgery, early mobilization was associated with an improvement in functional outcomes without an increase in surgical recurrence. These findings support the preference for an early mobilization protocol in cSDH patients over mandatory bed rest strategies.

Berberine alleviated contrast-induced acute kidney injury by mitophagy-mediated NLRP3 inflammasome inactivation in a mice model

The incidence of contrast-induced acute kidney injury (CI-AKI) has escalated to become the third most prevalent cause of hospital-acquired AKI, with a lack of efficacious interventions. Berberine (BBR) possesses diverse pharmacological effects and exhibits renoprotective properties; however, limited knowledge exists regarding its impact on CI-AKI. Therefore, our study aimed to investigate the protective effects and underlying mechanisms of BBR on CI-AKI in a mice model, focusing on the nucleotide-binding oligomerization domain-like pyrin domain-containing protein 3 (NLRP3) inflammasome and mitophagy. The CI-AKI mice model was established by administering NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg), indomethacin (10 mg/kg), and iohexol (11 g/kg) following water deprivation. A pretreatment of 100 mg/kg of BBR was orally administered to the mice for two weeks. Renal injury markers, damage-associated molecular patterns (DAMPs), renal histopathology, mitochondrial morphology, autophagosomes, and potential mechanisms were investigated. BBR effectively reduced levels of renal injury biomarkers such as serum cystatin C, urea nitrogen, and creatinine, downregulated the protein level of kidney injury molecule 1 (KIM1), and mitigated renal histomorphological damage. Moreover, BBR reduced DAMPs, including high mobility group box-1 (HMGB1), heat shock protein 70 (HSP70), and uric acid (UA). It also alleviated oxidative stress and inflammatory factors such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β). Furthermore, the activation of NLRP3 inflammasome was attenuated in the BBR pretreatment group, as evidenced by both mRNA and protein levels. Electron microscopy and western blotting examination revealed that BBR mitigated mitochondrial damage and enhanced mitophagy. Additionally, BBR increased the P-AMPK/AMPK ratio. These findings indicated that BBR exerted a protective effect against CI-AKI by suppressing NLRP3 inflammasome activation and modulating mitophagy, providing a potential therapeutic strategy for its prevention.

Circulating HMGB1 in acute ischemic stroke and its association with post-stroke cognitive impairment.

Ischemic stroke frequently leads to a condition known as post-stroke cognitive impairment (PSCI). Timely recognition of individuals susceptible to developing PSCI could facilitate the implementation of personalized strategies to mitigate cognitive deterioration. High mobility group box 1 (HMGB1) is a protein released by ischemic neurons and implicated in inflammation after stroke. Circulating levels of HMGB1 could potentially serve as a prognostic indicator for the onset of cognitive impairment following ischemic stroke. To investigate the predictive value of circulating HMGB1 concentrations in the acute phase of ischemic stroke for the development of cognitive dysfunction at the 3-month follow-up. A total of 192 individuals experiencing their initial episode of acute cerebral infarction were prospectively recruited for this longitudinal investigation. Concentrations of circulating HMGB1 were quantified using an enzyme-linked immunosorbent assay (ELISA) technique within the first 24 hours following hospital admission. Patients underwent neurological evaluation including NIHSS scoring. Neuropsychological evaluation was conducted at the 3-month follow-up after the cerebrovascular event, employing the Montreal Cognitive Assessment (MoCA) as the primary tool for assessing cognitive performance. Multivariable logistic regression models were employed to investigate the relationship between circulating HMGB1 concentrations and cognitive dysfunction following stroke, which was operationalized as a MoCA score below 26, while controlling for potential confounders including demographic characteristics, stroke severity, vascular risk factors, and laboratory parameters. Of 192 patients, 84 (44%) developed PSCI. Circulating HMGB1 concentrations were significantly elevated in individuals who developed cognitive dysfunction following stroke compared to those who maintained cognitive integrity (8.4 ±1.2 ng/mL vs 4.6 ±0.5 ng/mL, respectively; p<0.001). The prevalence of PSCI showed a dose-dependent increase with higher HMGB1 quartiles. After controlling for potential confounders such as demographic factors (age, gender, and education), stroke severity, vascular risk factors, and laboratory parameters in a multivariable logistic regression model, circulating HMGB1 concentrations emerged as a significant independent predictor of cognitive dysfunction following stroke (regression coefficient = 0.236, p<0.001). Circulating HMGB1 concentrations quantified within the first 24 hours following acute cerebral infarction are significantly and independently correlated with the likelihood of developing cognitive dysfunction at the 3-month follow-up, even after accounting for potential confounding factors. HMGB1 may be a novel biomarker to identify patients likely to develop post-stroke cognitive impairment for targeted preventive interventions.

Magnolia biondii flower extract attenuates UVB-induced skin damage through high-mobility group box protein B1.

Magnolia biondii, a plant containing many magnolian-like compounds in its flowers or buds, exhibits anti-inflammatory and antiallergic effects; however, no study has addressed its effect on alleviating ultraviolet light (UV)-induced skin damage. We thus aimed at studying the effects of M. biondii flower extract (MB) on UVB-induced skin damage and determine the relationship between cell damage and damage-associated molecular patterns (DAMPs). Reconstructed epidermal models and foreskin samples were selected to detect cellular reactions after UVB irradiation and MB treatment. MTT, haematoxylin-eosin and immunofluorescence staining were used to examine total viability, sunburned cells and expression and migration of DAMPs at 16 or 48 h. Prostaglandin E2 (PGE-2) and interleukin 8 (IL-8) levels were measured using enzyme-linked immunosorbent assays. A clinical UVB-damaged test was carried out on human arms subjected to MB pre- or post-treatment. Human skin probes were used to measure erythema, melanin, ITA° and transepidermal water loss (TEWL), while skin photos were captured using the VISIA system. MB is rich in lignans such as magnolin, pinoresinol dimethyl ether and fargesin, and shows weak UV absorption at 280-320 nm. Coculturing with MB for 16 or 48 h after UVB irradiation improved the tissue viability and structure of Skinovo-Epi, and reduced the expression and migration of high mobility group box protein B1 (HMGB1) as well as the expression of IL-8 and PGE-2. In the excised foreskin treated with MB after UVB irradiation, the generation of 8-hidroxy-2-deoxyguanosine and nuclear transfer of HMGB1 were reduced. When pre-treated with MB for 3 days, UVB-induced skin erythema and ITA° were significantly decreased. When post-treated with MB for 5 days, a decrease in skin erythema, melanin and TEWL values and an increase in skin ITA° were observed. Treatment with MB attenuated UVB-induced skin damage, such as erythema, pigmentation and skin barrier function, by improving the tissue viability and structure and reducing sunburned cells and skin inflammation. This effect may be related to DNA damage, which causes the migration of HMGB1 from the nucleus to the outside of the cell to induce skin inflammation.

Dynamic changes and clinic significance of serum high mobility group box 1 in patients with total hip arthroplasty

Dynamic changes and clinic significance of serum high mobility group box 1 in patients with total hip arthroplasty

Development of a group II intron-based genetic manipulation tool for Streptomyces.

The availability of an alternative and efficient genetic editing technology is critical for fundamental research and strain improvement engineering of Streptomyces species, which are prolific producers of complex secondary metabolites with significant pharmaceutical activities. The mobile group II introns are retrotransposons that employ activities of catalytic intron RNAs and intron-encoded reverse transcriptase to precisely insert into DNA target sites through a mechanism known as retrohoming. We here developed a group II intron-based gene editing tool to achieve precise chromosomal gene insertion in Streptomyces. Moreover, by repressing the potential competition of RecA-dependent homologous recombination, we enhanced site-specific insertion efficiency of this tool to 2.38%. Subsequently, we demonstrated the application of this tool by screening and characterizing the secondary metabolite biosynthetic gene cluster (BGC) responsible for synthesizing the red pigment in Streptomyces roseosporus. Accompanied with identifying and inactivating this BGC, we observed that the impair of this cluster promoted cell growth and daptomycin production. Additionally, we applied this tool to activate silent jadomycin BGC in Streptomyces venezuelae. Overall, this work demonstrates the potential of this method as an alternative tool for genetic engineering and cryptic natural product mining in Streptomyces species.

Effects of magnesium sulfate combined with labetalol on inflammatory stress and pregnancy outcome of patients with gestational hypertension.

Gestational hypertension (GH) is a common disorder during pregnancy that can cause adverse pregnancy outcomes. In the present study, magnesium sulfate (MgSO4) combined with labetalol was used for clinical treatment. Randomized controlled trial was conducted in 100 patients with GH, documented in the Department of Obstetrics and Gynecology (Taicang TCM Hospital) grouped into the experimental (Expt) and control (Ctrl) groups (n=50 cases/group). The Ctrl group was treated with MgSO4, whereas the Expt group was treated with MgSO4 + labetalol. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the Expt group were not significantly different from those in the Ctrl group (P>0.05). By contrast, the SBP and DBP were significantly lower after treatment than those before treatment in both groups (P<0.05). Whole blood viscosity, plasma viscosity and hematocrit were significantly lower in the Expt group compared with those in the Ctrl group after treatment (P<0.05). High mobility group box-1 protein, homocysteine and serum cystatin C levels in the Expt group were also markedly lower than those in the Ctrl group after treatment (P<0.05). In the Expt group, the rate of spontaneous vaginal delivery was much higher, whereas the rates of cesarean section and postpartum hemorrhage were markedly lower than those in the Ctrl group (P<0.05). The occurrence of fetal intrauterine distress, placental abruption, neonatal asphyxia, premature birth and neonatal death were also significantly lower in the Expt group than those in the Ctrl group (P<0.05). In conclusion, MgSO4 + labetalol could improve inflammatory stress and the hemodynamics of patients with GH, and may have a marked antihypertensive effect. Thus, it may improve pregnancy outcome and reduce perinatal complications.

Clinicopathological Significance and Prognostic Role of High Mobility Group Box 1 (HMGB1), Toll-Like Receptor (TLR) 2 and TLR4 in Breast Cancer.

High-mobility group box 1 (HMGB1) functions as damage-associated molecular pattern (DAMPs), released into extracellular space during cellular stress. Extracellular HMGB1 act as signal molecules through Toll-like receptor (TLR) 2 or TLR4, exerting diverse functions in both normal cells and malignant cells including breast cancer. However, their comprehensive examination in breast cancer tissues is lacking. Thus, we immunolocalized them in 112 breast cancer tissues, correlating their immunoreactivity with clinicopathological parameters and clinical outcomes to clarify their significance in breast cancer. We demonstrated that nuclear HMGB1 immunoreactivity was correlated with tumor progression and longer disease-free survival. In contrast, TLR2 immunoreactivity was correlated with increased cell proliferation and shorter disease-free survival, dependent on cytoplasmic HMGB1 immunoreactivity. Additionally, TLR4 immunoreactivity correlated with chemoresistance, regardless of cytoplasmic HMGB1 immunoreactivity. It was therefore considered that TLR2 collaboratively contributed to breast cancer progression with HMGB1-DAMPs to become a worse prognostic factor. Meanwhile, TLR4 served as a worse prognostic factor associated with chemoresistance, irrespective of HMGB1.

Multiple functions of HMGB1 in cancer.

High mobility group box 1 (HMGB1) is a nuclear DNA-binding protein with a dual role in cancer, acting as an oncogene and a tumor suppressor. This protein regulates nucleosomal structure, DNA damage repair, and genomic stability within the cell, while also playing a role in immune cell functions. This review comprehensively evaluates the biological and clinical significance of HMGB1 in cancer, including its involvement in cell death and survival, its potential as a therapeutic target and cancer biomarker, and as a prosurvival signal for the remaining cells after exposure to cytotoxic anticancer treatments. We highlight the need for a better understanding of the cellular markers and mechanisms involved in the involvement of HMGB1in cancer, and aim to provide a deeper understanding of its role in cancer progression.