Lung cancer is the world-leading causative factor of disease-related death. CD4+CD25+ regulatory T cells (CD4+CD25+ Treg), which are involved in immune escape of tumor cells, are highly related to ...tumor development and metastasis. Hypoxia induces the overexpression of chemokine (C-C motif) ligand 28 (CCL28), thus enhancing the angiogenesis and metastasis of lung adenocarcinoma. Our study revealed that most clinical lung adenocarcinoma samples showed positive expressions of HIF-lα, VEGF, FoxP3, and CCL28. More CD4+CD25+ Treg cells were detected in the cancerous samples. In addition, hypoxia increased the expression of HIF-1α and upregulated CCL28 to recruit CD4+CD25+ Treg cells; knockdown of HIF-1α could reverse this process. Treg cells also promoted invasion, migration, and angiogenesis in two human lung adenocarcinoma cell lines A549 and H1975. Our study suggested a novel potential molecular mechanism involved in the progression of lung adenocarcinoma could be a potential therapeutic target for the treatment of lung cancer.
Background
While tetracycline antibiotics are commonly prescribed in practice, the risk of drug-induced liver injury (DILI) remains controversial.
Aim
To evaluate the association of DILI with ...tetracycline antibiotics.
Method
All DILI cases of tetracycline antibiotics as primary suspected drugs were extracted from the US Food and Drug Administration adverse event reporting system (FAERS). The outcomes included severe DILI, hepatocellular injury, cholestatic injury, and liver failure. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC).
Results
A total of 1,435 liver injury cases associated with tetracycline antibiotics were identified. The DILI signal was detected in tigecycline, minocycline, and doxycycline. The RORs and the 95% confidence intervals (95% CI) of tigecycline, minocycline, and doxycycline were (ROR 5.85, 95% CI 4.96–6.91), (ROR 6.4, 95% CI 5.76–7.11), and (ROR 2.07, 95% CI 1.86–2.31), respectively. Compared to minocycline (ROR 5.5, 95% CI 4.94–6.12; IC 2.35, 95% CI 1.98–2.68) and doxycycline (ROR 1.91, 95% CI 1.71–2.12; IC 0.91, 95% CI 0.55–1.26), tigecycline showed a stronger association with hepatocellular injury (ROR 7.11, 95% CI 6.13–8.23; IC 2.68, 95% CI 2.16–3.13). Tigecycline also showed a stronger association with cholestatic injury (ROR 12.16, 95% CI 10.13–14.61; IC 3.51, 95% CI 2.79–4) than minocycline (ROR 3.23, 95% CI 2.59–4.04; IC 1.67, 95% CI 0.9–2.37) or doxycycline (ROR 2.86, 95% CI 2.47–3.31; IC 1.5, 95% CI 1–1.97). Tigecycline (ROR 6.56, 95% CI 4.57–9.41; IC 2.69, 95% CI 1.28–3.64) and minocycline (ROR 4.22, 95% CI 3.14–5.66; IC 2.06, 95% CI 1–2.93) showed a significant association with liver failure.
Conclusion
The data mining of FAERS suggested an association between DILI and tigecycline, minocycline, and doxycycline.
Endometriosis, an estrogen-dependent chronic inflammatory disease characterized by the growth of endometrium-like tissues outside the uterine cavity, affects 10% of reproductive-age women. Although ...the pathogenesis of endometriosis is uncertain, it is widely accepted that retrograde menstruation results in ectopic endometrial tissue implantation. Given that not all women with retrograde menstruation develop endometriosis, immune factors have been hypothesized to affect the pathogenesis of endometriosis. In this review, we demonstrate that the peritoneal immune microenvironment, including innate immunity and adaptive immunity, plays a central role in the pathogenesis of endometriosis. Current evidence supports the fact that immune cells, such as macrophages, natural killer (NK) cells, dendritic cells (DCs), neutrophils, T cells, and B cells, as well as cytokines and inflammatory mediators, contribute to the vascularization and fibrogenesis of endometriotic lesions, accelerating the implantation and development of ectopic endometrial lesions. Endocrine system dysfunction influences the immune microenvironment through overexpressed estrogen and progesterone resistance. In light of the limitations of hormonal therapy, we describe the prospects for potential diagnostic biomarkers and nonhormonal therapy based on the regulation of the immune microenvironment. Further studies are warranted to explore the available diagnostic biomarkers and immunological therapeutic strategies for endometriosis.
Legg-Calvé-Perthes disease or Perthes disease is a condition that occurs in children aged 2 to 15 years, and is characterized by osteonecrosis of the femoral head, which results in physical ...limitations. Despite ongoing research, the pathogenesis and molecular mechanisms underlying the development of Perthes disease remain unclear. In order to obtain further insights, the expression patterns of long non-coding RNAs (lncRNAs), miRNAs, and mRNAs in a rabbit model of Perthes disease were analyzed in this study by transcriptome sequencing.
The results of RNA-seq analyses revealed that 77 lncRNAs, 239 miRNAs, and 1027 mRNAs were differentially expressed in the rabbit model. This finding suggested that multiple genetic pathways are involved in the development of Perthes disease. A weighted gene co-expression network analysis (WGCNA) network was subsequently constructed using the differentially expressed mRNAs (DEmRNAs), and network analysis revealed that the genes associated with angiogenesis and platelet activation were downregulated, which was consistent with the findings of Perthes disease. A competing endogenous RNA (ceRNA) network was additionally constructed using 29 differentially expressed lncRNAs (including HIF3A and LOC103350994), 28 differentially expressed miRNAs (including ocu-miR-574-5p and ocu-miR-324-3p), and 76 DEmRNAs (including ALOX12 and PTGER2).
The results obtained herein provide novel perspectives regarding the pathogenesis and molecular mechanisms underlying the development of Perthes disease. The findings of this study can pave the way for the development of effective therapeutic strategies for Perthes disease in future.
Carboxylesterases (CXE) and methylesterases (MES) are hydrolytic enzymes that act on carboxylic esters and are involved in plant metabolic processes and defense responses. A few functions of plant
...and
genes have been identified but very little information is available about the role of most members. We made a comprehensive study of this gene family in a commercially important species, peach (
L. Batsch). A total of 33 peach
genes and 18
genes were identified and shown to be distributed unevenly between the chromosomes. Based on phylogenetic analysis, CXEs and MESs clustered into two different branches. Comparison of the positions of intron and differences in motifs revealed the evolutionary relationships between
and
genes. RNA-seq revealed differential expression patterns of
s in peach flower, leaf, and ripening fruit and in response to methyl jasmonate (MeJA) and ultraviolet B treatment. Transcript levels of candidate genes were verified by real-time quantitative PCR. Heterologous expression in
identified three CXEs that were involved in the hydrolysis of volatile esters
. Furthermore, two recombinant MES proteins were identified that could hydrolyze MeJA and methyl salicylate. Our results provide an important resource for the identification of functional
and
genes involved in the catabolism of volatile esters, responses to biotic and abiotic stresses and activation of signaling molecules such as MeJA and methyl salicylate.
Background. The 5-year overall survival rate of ovarian cancer (OC) patients is less than 40%. Hypoxia promotes the proliferation of OC cells and leads to the decline of cell immunity. It is crucial ...to find potential predictors or risk model related to OC prognosis. This study aimed at establishing the hypoxia-associated gene signature to assess tumor immune microenvironment and predicting the prognosis of OC. Methods. The gene expression data of 378 OC patients and 370 OC patients were downloaded from datasets. The hypoxia risk model was constructed to reflect the immune microenvironment in OC and predict prognosis. Results. 8 genes (AKAP12, ALDOC, ANGPTL4, CITED2, ISG20, PPP1R15A, PRDX5, and TGFBI) were included in the hypoxic gene signature. Patients in the high hypoxia risk group showed worse survival. Hypoxia signature significantly related to clinical features and may serve as an independent prognostic factor for OC patients. 2 types of immune cells, plasmacytoid dendritic cell and regulatory T cell, showed a significant infiltration in the tissues of the high hypoxia risk group patients. Most of the immunosuppressive genes (such as ARG1, CD160, CD244, CXCL12, DNMT1, and HAVCR1) and immune checkpoints (such as CD80, CTLA4, and CD274) were upregulated in the high hypoxia risk group. Gene sets related to the high hypoxia risk group were associated with signaling pathways of cell cycle, MAPK, mTOR, PI3K-Akt, VEGF, and AMPK. Conclusion. The hypoxia risk model could serve as an independent prognostic indicator and reflect overall immune response intensity in the OC microenvironment.
Tetracentron sinense Oliv. is an endangered relict tree found in south-central China. A low number of seedlings among the natural populations has resulted in the poor regeneration of this species. ...However, the mechanisms underlying seedling survival and growth remain poorly understood. Leaf functional traits (LFT) likely characterize the growth and development of T. sinense in different ecological environments, playing a crucial role in its adaptive strategies to adversity. In this study, two-factor orthogonal control experiments with two levels of light intensity (L1: 50 % natural light intensity in forest edge; L2: 10 % natural light intensity in understory) and soil moisture content (W1: 30 % moisture content in valley; W2: 15 % moisture content in mountainside) were conducted to analyze the response of the LFT of 7-month-old T. sinense seedlings to different light and soil moisture conditions. With the light intensity decreased, superoxide dismutase activity decreased, and peroxidase activity increased. With a decrease in soil moisture, the contents of chlorophyll (Chl) a, Chl b, Chl t, and soluble sugar increased, and Chl a/b decreased. A decrease in light and soil moisture decreased leaf thickness, leaf dry weight, leaf dry matter content, leaf volume, chloroplast volume, and starch grains, but increased osmophilic grains, the total nitrogen, and phosphorus contents. Moreover, the chloroplast morphology of L2W2 was more complete than that of other treatments. The results showed that the LFT of T. sinense seedlings acted synergistically to adapt to different light and soil moisture conditions, low soil moisture alleviated the effects of shading in T. sinense seedlings, and T. sinense seedlings adopted the “quick investment-return strategy” adaptation strategy under L2W2. Finally, the soil moisture of the mountainside in the natural habitat was favorable to the survival and growth of T. sinense seedlings.
Background The medication regimen for critically ill patients is complex and dynamic, leading to a high incidence of drug-related problems. This study aimed to assess the effectiveness and economic ...efficiency of pharmaceutical care for these patients. Methods In this prospective cohort study conducted in a tertiary hospital, adult patients were assigned either to a clinical pharmaceutical care group or a control group based on existing clinical grouping rules. Health outcomes and economic indicators were collected, followed by a cost-effectiveness analysis. Results The acceptance rate for clinical pharmacist interventions was 89.31%. The pharmaceutical care group exhibited significant reductions in the rate of medication errors (40.65% vs. 61.69%, P < 0.001) and adverse drug events (44.52% vs. 56.45%, P = 0.020). The usage rates for special-grade antibiotics (85.16% vs. 91.13%, P = 0.009) and proton pump inhibitors (77.42% vs. 88.71%, P = 0.002) were also lower in the pharmaceutical care group. Secondary outcomes did not show significant differences in total hospital stay (21 days vs. 22 days, P = 0.092). However, ICU stay was significantly shorter (9 days vs. 11 days, P = 0.003) in the pharmaceutical care group. Cost-effectiveness analysis demonstrated that each 1% reduction in adverse drug events associated with ICU pharmaceutical care saved $226.75 in ICU hospitalization costs and $203.42 in total ICU drug costs. A 1% reduction in the medication error rate saved $128.57 in ICU hospitalization costs and $115.34 in total ICU drug costs. Conclusions Pharmaceutical care significantly reduces adverse drug events and medication errors, promotes rational use of medications, decreases the length of ICU stay, and lowers treatment costs in critically ill patients, establishing a definitive advantage in terms of cost-effectiveness.
This study aimed to investigate the efficacy of rTMS in the treatment of poststroke epilepsy and the effect of rTMS on patients' cognitive function and depressive status.
One hundred and twenty-one ...poststroke epilepsy patients with mild cognitive impairment and depressive status admitted to the Department of Neurology of the Second People's Hospital of Nanning from January 1, 2017, to April 31, 2023, were selected and divided into the rTMS treatment group (treated group) and the control group. MMSE scores and HAMD scores were recorded before and after treatment. The frequency of EEG spiky waves recorded before and after treatment within 24 h and the frequency of any clinical seizure form (the number of clinical seizures within 1 month after treatment) and changes in observed indices before and after treatment were calculated. The differences between the data of the two groups were analyzed, to further assess the efficacy of rTMS in the treatment of poststroke epilepsy and the rTMS' effects on cognition and depression.
Compared with drug treatment alone, rTMS significantly decreased clinical seizures and epileptiform discharges after stroke, especially in patients with lesions in the frontal, temporal, and parietal lobes. Compared with drug treatment alone, rTMS treatment can effectively reduce cognitive impairment and mood disorders, such as depression, especially for patients with lesions in the frontal and temporal lobes. The results of this experiment suggest that rTMS treatment does not increase adverse effects.
rTMS reduces clinical seizures while improving cognitive impairment and depression in patients with epilepsy. Therefore, we suggest that low-frequency rTMS can be used as an adjunctive treatment for patients with epilepsy and provide some ideas and references for the treatment of epilepsy with cognitive impairment and depression.
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