Targeting tumor-associated macrophage: an adjuvant strategy for lung cancer therapy.

The emergence of immunotherapy has revolutionized the treatment landscape for various types of cancer. Nevertheless, lung cancer remains one of the leading causes of cancer-related mortality worldwide due to the development of resistance in most patients. As one of the most abundant groups of immune cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play crucial and complex roles in the development of lung cancer, including the regulation of immunosuppressive TME remodeling, metabolic reprogramming, neoangiogenesis, metastasis, and promotion of tumoral neurogenesis. Hence, relevant strategies for lung cancer therapy, such as inhibition of macrophage recruitment, TAM reprograming, depletion of TAMs, and engineering of TAMs for drug delivery, have been developed. Based on the satisfactory treatment effect of TAM-targeted therapy, recent studies also investigated its synergistic effect with current therapies for lung cancer, including immunotherapy, radiotherapy, chemotherapy, anti-epidermal growth factor receptor (anti-EGFR) treatment, or photodynamic therapy. Thus, in this article, we summarized the key mechanisms of TAMs contributing to lung cancer progression and elaborated on the novel therapeutic strategies against TAMs. We also discussed the therapeutic potential of TAM targeting as adjuvant therapy in the current treatment of lung cancer, particularly highlighting the TAM-centered strategies for improving the efficacy of anti-programmed cell death-1/programmed cell death-ligand 1 (anti-PD-1/PD-L1) treatment.

PHLDA1 modulates microglial response and NLRP3 inflammasome signaling following experimental subarachnoid hemorrhage.

Balancing microglia M1/M2 polarization is an effective therapeutic strategy for neuroinflammation after subarachnoid hemorrhage (SAH). Pleckstrin homology-like domain family A member 1 (PHLDA1) has been demonstrated to play a crucial role in immune response. However, the function roles of PHLDA1 in neuroinflammation and microglial polarization after SAH remain unclear. In this study, SAH mouse models were assigned to treat with scramble or PHLDA1 small interfering RNAs (siRNAs). We observed that PHLDA1 was significantly increased and mainly distributed in microglia after SAH. Concomitant with PHLDA1 activation, nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome expression in microglia was also evidently enhanced after SAH. In addition, PHLDA1 siRNA treatment significantly reduced microglia-mediated neuroinflammation by inhibiting M1 microglia and promoting M2 microglia polarization. Meanwhile, PHLDA1 deficiency reduced neuronal apoptosis and improved neurological outcomes after SAH. Further investigation revealed that PHLDA1 blockade suppressed the NLRP3 inflammasome signaling after SAH. In contrast, NLRP3 inflammasome activator nigericin abated the beneficial effects of PHLDA1 deficiency against SAH by promoting microglial polarization to M1 phenotype. In all, we proposed that PHLDA1 blockade might ameliorate SAH-induced brain injury by balancing microglia M1/M2 polarization via suppression of NLRP3 inflammasome signaling. Targeting PHLDA1 might be a feasible strategy for treating SAH.

A research review of experimental animal models with myelodysplastic syndrome

Myelodysplastic syndrome (MDS) consists of a group of hematologic tumors that are derived from the clonal proliferation of hematopoietic stem cells, featuring abnormal hematopoietic cell development and ineffective hematopoiesis. Animal models are an important scientific research platform that has been widely applied in the research of human diseases, especially tumors. Animal models with MDS can simulate characteristic human genetic variations and tumor phenotypes. They also provide a reliable platform for the exploration of the pathogenesis and diagnostic markers of MDS as well as for a drug efficacy evaluation. This paper reviews the research status of three animal models and a new spontaneous mouse model with MDS (AU)

A research review of experimental animal models with myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) consists of a group of hematologic tumors that are derived from the clonal proliferation of hematopoietic stem cells, featuring abnormal hematopoietic cell development and ineffective hematopoiesis. Animal models are an important scientific research platform that has been widely applied in the research of human diseases, especially tumors. Animal models with MDS can simulate characteristic human genetic variations and tumor phenotypes. They also provide a reliable platform for the exploration of the pathogenesis and diagnostic markers of MDS as well as for a drug efficacy evaluation. This paper reviews the research status of three animal models and a new spontaneous mouse model with MDS.

[Expression of SIL-2R in Patients with Multiple Myeloma and Its Clinical Significance].

OBJECTIVE: To investigate the expression and clinical significance of soluble interleukin-2 receptor(sIL-2R) in patients with multiple myeloma(MM). METHODS: 54 newly diagnosed MM patients in the Second Affiliated Hospital of Fujian Medical University from February 2020 to December 2021 were selected as the observation group, and 60 healthy people in our hospital in the same period were selected as the control group. The expression levels of sIL-2R in the serum of the two groups were detected by enzyme-linked immunosorbent assay. The differences of sIL-2R expression level among different clinical parameter groups in MM patients were compared. The clinical parameters include:gender, age, ISS stage, hemoglobin, albumin, serum creatinine, lactate dehydrogenase and ß2-microglobulin, blood calcium, bone marrow plasma cell ratio and treatment response. The relationship between sIL-2R expression level and progression-free survival(PFS) and overall survival(OS) in MM patients were analyzed. RESULTS: The expression of serum SIL-2R in MM patients was significantly higher than that in healthy control group (P<0.05). The expression of sIL-2R in MM patients who did not achieve complete remission(CR) was significantly higher than those of CR patients (P=0.037). There was no significant difference in the expression of serum sIL-2R between the groups of different sex, age, ISS stage, hemoglobin concentration, albumin content, serum creatinine level, lactate dehydrogenase level, the content of ß2-microglobulin, the concentration of blood calcium, and the proportion of bone marrow plasma cells(P>0.05). The PFS of sIL-2R high expression group(15 months) was shorter than that of sIL-2R low expression group (22 months), which was significant difference (P=0.041). But there was no significant difference in OS between sIL-2R high expression group and sIL-2R low expression group (P=0.124). Univariate analysis results showed that the high expression of serum sIL-2R was associated with poor PFS in MM patients. Multivariate analysis results showed that the high expression of serum sIL-2R was still an independent adverse prognostic factor for PFS in MM patients, However, the expression of serum sIL-2R was not statistically significant in evaluating OS in MM patients by univariate and multivariate analysis. CONCLUSION: The expression of serum sIL-2R in MM patients was significantly higher than that in healthy people. Serum sIL-2R is an independent prognostic factor of PFS in MM patients.

DNA walker-amplified signal-on electrochemical aptasensors for prostate-specific antigen coupling with two hairpin DNA probe-based hybridization reaction.

Electrochemical aptasensing systems have been developed for screening low-abundance disease-related proteins, but most of them involve multiple washings and multi-step separation during measurements, and thus are disadvantageous for routine use. In this work, an innovative and simple electrochemical aptasensing platform was designed for the voltammetric detection of prostate-specific antigen (PSA) in biological fluids without any washing and separation steps. This system mainly included a PSA-specific aptamer, a DNA walker and two hairpin DNA probes (i.e., thiolated hairpin DNA1 and ferrocene-labeled hairpin DNA2). Introduction of target PSA caused the release of the DNA walker from a partially complementary aptamer/DNA walker hybridization strand. The dissociated DNA walker opened the immobilized hairpin DNA1 on the electrode, accompanying subsequent displacement reaction with hairpin DNA2, thus resulting in the DNA walker step-by-step reaction with numerous hairpin DNA1 probes on the sensing interface. In this case, numerous ferrocene molecules were close to the electrode to amplify the voltammetric signal within the applied potentials. All reactions and electrochemical measurements including the target/aptamer reaction and hybridization chain reaction were implemented in the same detection cell. Under optimal conditions, the fabricated electrochemical aptasensor gave good voltammetric responses relative to the PSA concentrations within the range of 0.001-10 ng mL-1 at an ultralow detection limit of 0.67 pg mL-1. A good reproducibility with batch-to-batch errors was acquired for target PSA down to 11.5%. Non-target analytes did not interfere with the voltammetric signals of the electrochemical aptasensors. Meanwhile, 15 human serum specimens were measured with electrochemical aptasensors, and displayed well-matched results in comparison with the referenced human PSA enzyme-linked immunosorbant assay (ELISA) method. Significantly, this method provides a new horizon for the quantitative monitoring of low-concentration biomarkers or nucleic acids.

The changes in pyroptosis-related inflammatory factors in the peripheral blood of patients with Henoch-Schonlein purpura.

BACKGROUND: Henoch-Schonlein purpura (HSP) is a common capillary allergic bleeding disease. To explore the variation of pyroptosis-related inflammatory factors level in the peripheral blood of patients with HSP. METHODS: A total of 87 HSP patients treated in our hospital from June 2020 to March 2021 were selected and divided into the renal impairment group (n=29) and the non-renal impairment group (n=58) according to the presence of hematuria and proteinuria. A total of 50 healthy individuals from the hospital were selected as the control group. The renal impairment and non-renal impairment groups were treated with a regular regimen of compound glycyrrhizin tablets and glucocorticoids, respectively. Serum interleukin (IL)-18, IL-1ß, and peripheral caspase-1-positive cells were compared pre- and post-treatment among the three groups. RESULTS: The pre-treatment serum IL-1ß levels in the renal impairment and non-renal impairment groups were significantly higher than that in the control group (P<0.01). After treatment, the IL-1ß level in the non-renal impairment group was not significantly different from that in the control group (P>0.05). However, the IL-1ß level in the renal impairment group post-treatment was significantly higher than that in the other two groups (P<0.01). The positive rate of caspase-1 expression in peripheral blood before treatment in the renal impairment group and non-renal impairment group was significantly higher than that in the control group (P<0.01). After treatment, the positive rate of caspase-1 expression in the non-renal impairment group was comparable to that in the control group (P>0.05), whereas the rate in the renal impairment group was significantly higher than that in the other two groups (P<0.01). After treatment, the serum IL-1ß levels and caspase-1 positive rate in HSP patients who were responsive to treatment (as assessed by hematuria or proteinuria levels after treatment) were lower than that in patients who were unresponsive to treatment P<0.001), but not significantly different to the control group (P>0.05). CONCLUSIONS: The levels of serum IL-1ß and caspase-1 changed in response to alterations in the disease condition and treatment response in HSP patients, which suggested that pyroptosis-related inflammatory factors may have potential application value in predicting disease progression and efficacy of hormone therapy.

Serum concentration of uric acid associated with prehypertension among Chinese population.

We evaluated the association between serum uric acid (SUA) levels and prehypertension in a Chinese population. A cross-sectional study was performed during 2008 to 2010, and a total of 11199 participants without hypertension or other cardiovascular diseases (CADs), aged ≥35 years, were available for analysis. After adjusting for age, alcohol consumption, smoking status, body mass index, diabetes, total cholesterol, triglycerides, serum creatinine, the odds ratios (ORs) and 95% confidence intervals (CIs) of the prehypertension from the lowest (referent) to the highest levels of SUA were 1.00 (95% CI, 0.91-1.10), 1.12 (95% CI, 1.03-1.21), 1.17 (95% CI, 1.09-1.27), and 1.25 (95% CI, 1.13-1.39; linear trend P = .002). This association persisted in subgroup analysis by gender and was also consistent with separate analysis by classification of age, smoking status, alcohol usage, overweight, and diabetes mellitus. Independent of other cardiovascular risk factors, higher SUA levels are positively associated with prehypertension in a Chinese population without hypertension and CADs. Prospective trials should evaluate interventions that lower the SUA levels.

Indoor solid fuel use and tuberculosis in China: a matched case-control study.

BACKGROUND: China ranks second among the 22 high burden countries for tuberculosis. A modeling exercise showed that reduction of indoor air pollution could help advance tuberculosis control in China. However, the association between indoor air pollution and tuberculosis is not yet well established. A case control study was conducted in Anhui, China to investigate whether use of solid fuel is associated with tuberculosis. METHODS: Cases were new sputum smear positive tuberculosis patients. Two controls were selected from the neighborhood of each case matched by age and sex using a pre-determined procedure. A questionnaire containing demographic information, smoking habits and use of solid fuel for cooking or heating was used for interview. Solid fuel (coal and biomass) included coal/lignite, charcoal, wood, straw/shrubs/grass, animal dung, and agricultural crop residue. A household that used solid fuel either for cooking and (/or) heating was classified as exposure to combustion of solid fuel (indoor air pollution). Odds ratios and their corresponding 95% confidence limits for categorical variables were determined by Mantel-Haenszel estimate and multivariate conditional logistic regression. RESULTS: There were 202 new smear positive tuberculosis cases and 404 neighborhood controls enrolled in this study. The proportion of participants who used solid fuels for cooking was high (73.8% among cases and 72.5% among controls). The majority reported using a griddle stove (85.2% among cases and 86.7% among controls), had smoke removed by a hood or chimney (92.0% among cases and 92.8% among controls), and cooked in a separate room (24.8% among cases and 28.0% among controls) or a separate building (67.8% among cases and 67.6% among controls). Neither using solid fuel for cooking (odds ratio (OR) 1.08, 95% CI 0.62-1.87) nor using solid fuel for heating (OR 1.04, 95% CI 0.54-2.02) was significantly associated with tuberculosis. Determinants significantly associated with tuberculosis were household tuberculosis contact (adjusted OR, 27.23, 95% CI 8.19-90.58) and ever smoking tobacco (adjusted OR 1.64, 96% CI 1.01-2.66). CONCLUSION: In a population where the majority had proper ventilation in cooking places, the association between use of solid fuel for cooking or for heating and tuberculosis was not statistically significant.