Effect of protective lung ventilation on pulmonary complications after laparoscopic surgery: a meta-analysis of randomized controlled trials.

Introduction: Compared with traditional open surgery, laparoscopic surgery is widely used in surgery, with the advantages of being minimally invasive, having good cosmetic effects, and having short hospital stays, but in laparoscopic surgery, pneumoperitoneum and the Trendelenburg position can cause complications, such as atelectasis. Recently, several studies have shown that protective lung ventilation strategies are protective for abdominal surgery, reducing the incidence of postoperative pulmonary complications (PPCs). Ventilator-associated lung injury can be reduced by protective lung ventilation, which includes microtidal volume (4-8 mL/kg) ventilation and positive end-expiratory pressure (PEEP). Therefore, we used randomized, controlled trials (RCTs) to assess the results on this topic, and RCTs were used for meta-analysis to further evaluate the effect of protective lung ventilation on pulmonary complications in patients undergoing laparoscopic surgery. Methods: In this meta-analysis, we searched the relevant literature contained in six major databases-CNKI, CBM, Wanfang Medical, Cochrane, PubMed, and Web of Science-from their inception to October 15, 2022. After screening the eligible literature, a randomized, controlled method was used to compare the occurrence of postoperative pulmonary complications when a protective lung ventilation strategy and conventional lung ventilation strategy were applied to laparoscopic surgery. After statistical analysis, the results were verified to be statistically significant. Results: Twenty-three trials were included. Patients receiving protective lung ventilation were 1.17 times less likely to develop pulmonary complications after surgery than those receiving conventional lung ventilation (hazard ratio [RR] 0.18, 95% confidence interval [CI] 1.13-1.22; I2 = 0%). When tested for bias (P = 0.36), the result was statistically significant. Patients with protective lung ventilation were less likely to develop pulmonary complications after laparoscopic surgery. Conclusion: Compared with conventional mechanical ventilation, protective lung ventilation reduces the incidence of postoperative pulmonary complications. For patients undergoing laparoscopic surgery, we suggest the use of protective lung ventilation, which is effective in reducing the incidence of lung injury and pulmonary infection. Implementation of a low tidal volume plus moderate positive end-expiratory pressure strategy reduces the risk of postoperative pulmonary complications.

Effect and mechanism of Salicornia bigelovii Torr. plant salt on blood pressure in SD rats.

In this paper, the effect and mechanism of Salicornia bigelovii Torr. plant salt (SPS) on blood pressure in Sprague Dawley (SD) rats were investigated. The results showed that the edible salt induced hypertension, but the SPS did not. Organ indices and Hematoxylin-Eosin (HE) staining analysis indicated that SPS had a protective effect on the kidney and liver. In comparison with the edible salt-treated group, nitric oxide (NO) content, angiotensin-II (Ang-II) and endothelin-1 (ET-1) levels in the serum of the SPS-treated group had no obvious changes, but serum creatinine concentration significantly decreased. Moreover, superoxide dismutase (SOD) and Na(+)-K(+)-ATPase activity increased while malondialdehyde (MDA) content decreased in the SPS-treated group. In conclusion, a long-term high salt intake could lead to hypertension. SPS, as a salt substitute, could increase the body's antioxidant ability to protect the kidney and liver from the damage caused by a high salt intake and effectively avoid the occurrence of hypertension.

Cancer stem cell targeting: the next generation of cancer therapy and molecular imaging.

Cancer stem cells (CSCs) have the capacity to generate the heterogeneous lineages of all cancer cells comprising a tumor and these populations of cells are likely to be more relevant in determining prognosis. However, these cells do not operate in isolation, but instead rely upon signals co-opted from their microenvironment, making the targeting and imaging of CSCs within a cancer mass a daunting task. A better understanding of the molecular cell biology underlying CSC pathology will facilitate the development of new therapeutic targets and novel strategies for the successful eradication of cancer. In addition, the continued investigation of sensitive molecular-imaging modalities will enable more accurate staging, treatment planning and the ability to monitor the effectiveness of CSC-targeted therapies in vivo. In this review, we explore the possibilities and limitations of CSC-directed therapies and molecular imaging modalities.

Clinical applications of aptamers and nucleic acid therapeutics in haematological malignancies.

Haematological malignancies result from a heterogeneous mix of genetic mutations and chromosome aberrations and translocations. Targeted therapies, such as the anti-CD20 antibody rituximab, or the BCR-ABL1 inhibitor imatinib, have proven to be effective treatments in the management of some of these malignancies, though relapsing or refractory disease is still common. Nucleic acid-based therapies have also entered the clinical arena, providing an alternative, complementary approach. The forerunner of these therapies were the antisense oligonucleotides, but their scope has expanded to include short-interfering RNA (siRNA), microRNA, decoy oligonucleotides and aptamers. These can be used either as mono-therapeutics, in conjunction with current chemotherapy regimens, or in combination with each other to improve therapeutic efficacy. Not only can these nucleic acid-based therapies silence target genes, they also have the potential of restoring gene function. While challenges remain in delivering effective doses of nucleic acid in vivo, these are steadily being met, suggesting an optimistic future in the treatment of haematological malignancies. This review summarizes the application of nucleic acid-based therapeutics, particularly aptamers, in the diagnosis and treatment of haematological malignancies.

Micro-RNA-21 regulates TGF-ß-induced myofibroblast differentiation by targeting PDCD4 in tumor-stroma interaction.

Transforming growth factor-ß1 (TGF-ß1) induces stromal fibroblast-to-myofibroblast transdifferentiation in the tumor-stroma interactive microenvironment via modulation of multiple phenotypic and functional genes, which plays a critical role in tumor progression. Up to now, the involvement of micro-RNAs (miRNAs) and their roles in TGF-ß1-induced myofibroblast differentiation in tumor-stroma interaction are unclear. Using quantitative real-time RT-PCR, we demonstrated that the expression of micro-RNA-21 (miR-21) was upregulated in activated fibroblasts after treatment with TGF-ß1 or conditioned medium from cancer cells. To determine the potential roles of miR-21 in TGF-ß1-mediated gene regulation during myofibroblast conversion, we showed that miR-21 expression was downregulated by miR-21 inhibitor and upregulated by miR-21 mimic. Interestingly, downregulation of miR-21 with the inhibitor effectively inhibited TGF-ß1-induced myofibroblast differentiation while upregulation of miR-21 with a mimic significantly promoted myofibroblast differentiation. We further demonstrated that MiR-21 directly targeted and downregulated programmed cell death 4 (PDCD4) gene, which in turn acted as a negative regulator of several phenotypic and functional genes of myofibroblasts. Taken together, these results suggested that miR-21 participated in TGF-ß1-induced myofibroblast transdifferentiation in cancer stroma by targeting PDCD4.

Turn a diarrhoea toxin into a receptor-mediated therapy for a plethora of CLDN-4-overexpressing cancers.

Molecular targeted therapy (MTT) represents the new generation of anti-cancer arsenals. In this study, we report an alternative approach using a hybrid toxin that utilises the high-affinity of receptor-binding fragment of Clostridium perfringens enterotoxin (CPE). CPE naturally binds to CLDN-4 through the C-terminal 30 amino acid. However, recent studies have shown that CLDN-4 is also overexpressed on a range of cancer cells. We thus constructed a cDNA comprising C-CPE and a well characterised toxic domain of Pseudomonas aeruginosa exotoxin A (C-CPE-ETA'). The recombinant C-CPE-ETA' fusion protein was shown to retain the specificity of binding to CLDN-4 and initiating rapid penetration into cytosol in five different CLDN-4 positive cancer cells (Breast-MCF7, Skin-A431, Colon-SW480, Prostate-PC3 and DU145) but not to CLDN-4 negative cells (Hela, HUVEC). C-CPE-ETA' was strongly cytotoxic towards CLDN-4 positive cancer cell, as opposed to cells lacking CLDN-4 expression. Furthermore, we demonstrated that the recombinant fusion protein had significant anti-cancer ability in CLDN-4 positive cancer models in vivo. Subcutaneously implanted MCF7 and SW480 xenograft tumours were significantly decreased or abolished after three repeated injection of the hybrid toxin. Taken together, our results convincingly show that the hybrid toxin targets CLDN-4 positive cancer through receptor-binding, and causes significant tumour cell apoptosis, suggesting its potential as an alternative molecular targeted therapy against a plethora of CLDN-4 positive cancers.

Combination of a fluorescent dye and a Zn-S cluster and its biological application as a stain for bacteria.

An ionic-pair charge-transfer salt [C(15)H(16)N(3)](+)[Zn(8)S(SC(6)H(5))(15).H(2)O](-) (1) featuring a fluorescent dye and a wurtzite-like octanuclear Zn-S cluster shows high stability when staining bacteria Escherichia coli, Salmonella typhimurium, and Clostridium novyi NT.

[Target-specific cytotoxic activity of recombinant fusion toxin C-CPE-ETA' against CLDN-3,4-overexpressing ovarian cancer cells].

OBJECTIVE: The aim of this study was to explore the possibility of creating a toxin, C-CPE-ETA', by fusing C-terminal high affinity binding domain of CPE (C-CPE) with a truncated form of Pseudomonas aeruginosa exotoxin A (ETA') and to examine whether C-CPE-ETA' could specifically target CLDN-3, 4 molecule and the targeted toxin was cytotoxic against CLDN-3,4-overexpressing ovarian cancer. METHODS: CLDN-3 and CLDN-4 expressions were analyzed at the mRNA level in three ovarian cancer cell lines and epithelial ovarian cancer tissues from 20 patients. After transforming an expression plasmid of C-CPE-ETA' into E. coli BL21 (DE3) plysS strain, the recombinant protein was purified using His-Bind resin chromatography column and analyzed by Western blot and Coomassie blue staining. The specific binding, proapoptotic and cytolytic activities were evaluated by flow cytometry, fluorescence microscopy with the JC-1 probe and MTT assay in CLDN-3,4-overexpressing ovarian cancer cells. RESULTS: Quantitive RT-PCR results showed there existed high levels of CLDN-3 and CLDN-4 in ovarian cancer cells, CAOV3, OVCAR3 and SKOV3. Moreover, high expressions of CLDN-3 and CLDN-4 were observed in 90.0% (18/20) and 60.0% (12/20) of ovarian cancer tissues, with an expression level 10-fold higher than that in the normal ovarian tissue. A 58 000 recombinant protein C-CPE-ETA' was demonstrated by Western blot and Coomassie blue staining. Purified and recombinant C-CPE-ETA' was bound with high affinity to CLDN-3,4-overexpressing ovarian cancer cells, CAOV3, OVCAR3 and SKOV3 cells. C-CPE-ETA' was strongly proapoptotic and cytotoxic towards the CLDN-3,4-overexpressing ovarian cancer cells. The concentration of IC(50) was 7.364 ng/ml for CAOV3 cells, 8.110 ng/ml for OVCAR3 cells and 22.340 ng/ml for SKOV3 cells, respectively. However, control CLDN-3,4-deficient cell line HUVEC was not susceptible to the recombinant C-CPE-ETA' at a concentration up to 10 µg/ml. CONCLUSIONS: The C-CPE-ETA' protein exhibits remarkably specific cytotoxicity for CLDN-3,4-overexpressing ovarian cancer cells. Its therapeutic potential warrants further development for ovarian cancer molecular targeted therapy.

CLIC4 mediates TGF-beta1-induced fibroblast-to-myofibroblast transdifferentiation in ovarian cancer.

Stromal myofibroblasts, activated by crosstalk signaling between the tumour and stroma, play a critical role in tumour development and progression. Chloride intracellular channel 4 (CLIC4) may be functionally import for tumour stromal fibroblast-to-myofibroblast transdifferentiaton, but the molecular mechanism of the process has not been addressed. In this study, the expression of CLIC4 in ovarian cancer tissues was analyzed by immunohistochemistry, and we used an indirect co-culture model of ovarian cancer cells and normal fibroblasts to demonstrate the molecular pathway in which CLIC4 participated during the fibroblast-to-myofibroblast transdifferentiation. The results showed that the expression of CLIC4 in 96.7% of ovarian cancer stroma and correlated with the up-regulation of myofibroblast marker alpha-SMA. Conditioned medium from ovarian cancer cells (CM) or transforming growth factor-beta1 (TGF-beta1) increased cellular reactive oxygen species (ROS) levels in fibroblasts, which initiated up-regulation of CLIC4 expression, then resulted in myofibroblast conversion. Moreover, inhibition of CLIC4 significantly reduced the expressions of factors related to the phenotype and functions of myofibroblasts, such as alpha-SMA, VEGF and HGF. These results suggest that ROS-initiated CLIC4 up-regulation is required for TGF-beta1-induced fibroblast-to-myofibroblast transdifferentiaton in ovarian cancer, indicating that inhibiting the CLIC4 might have therapeutic potential targeting tumour stroma.