Molecular cloning, codon-optimized gene expression, and bioactivity assessment of two novel fungal immunomodulatory proteins from Ganoderma applanatum in Pichia.

Fungal immunomodulatory proteins (FIPs) have been identified from a series of fungi, especially in Ganoderma species. However, little is known about the FIPs from G. applanatum. In this study, two novel FIP genes, termed as FIP-gap1 and FIP-gap2, were cloned from G. applanatum, characterized and functionally expressed after codon optimization in Pichia pastoris GS115. Results showed that FIP-gap1 and FIP-gap2 comprised 342-bp encoding peptides of 113 amino acids, which shared a high homology with other Ganoderma FIPs. The yield of recombinant FIP-gap1 and FIP-gap2 increased significantly after codon optimization and reached 247.4 and 197.5 mg/L, respectively. Bioactivity assay in vitro revealed that both rFIP-gap1 and rFIP-gap2 could agglutinate mouse, sheep, and human red blood cells. Besides, rFIP-gap1 and rFIP-gap2 obviously stimulated the proliferation of mouse splenocytes and enhanced IL-2 and IFN-γ release. Cytotoxicity detection indicated that IC50 of rFIP-gap1 towards A549 and HeLa cancer cells were 29.89 and 8.34 µg/mL, respectively, whereas IC50 of rFIP-gap2 to the same cancer cells were 60.92 and 41.05 µg/mL, respectively. Taken together, novel FIP gaps were cloned and functionally expressed in P. pastoris, which can serve as feasible and stable resources of rFIP gaps for further studies and potential applications.

Efficacy and safety evaluation of mixed nutrition for postoperative esophageal cancer patients in China: a meta-analysis.

Objective: The purpose of this study was to evaluate the clinical effect of mixed nutrition and parenteral nutrition support on postoperative patients with esophageal cancer. Method: By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures until March 2024 about the comparison of randomized controlled Trial (RCT) of mixed nutrition and parenteral nutrition support in postoperative patients with esophageal cancer were screened. The inclusion criteria were that the patients were from randomized controlled trials or clinical trials in China, and the patients were all diagnosed with esophageal cancer by pathological biopsy. The exclusion criteria were the literature other than the above, including repeated published literature, non-Chinese and English literature, incomplete or missing analysis data, etc. After two researchers independently screened the literature, extracted the data and evaluated the risk of bias according to the criteria, Meta-analysis was carried out with RevMan 5.4 software. Results: A total of 11 studies were included, including 1216 patients. Meta-analysis showed that, compared with parenteral nutrition, mixed nutrition can improve the levels of transferrin, serum albumin, prealbumin and lymphocyte counts in patients with esophageal cancer after surgery, shorten the time of anal recovery of exhaust, defecation and hospital stay after surgery, and reduce the incidence of pulmonary infection, abdominal distension, incision infection and anastomotic fistula, with statistical significance between the two groups (P < 0.05). The heterogeneity of individual results in this study is relatively high, the analysis comes from clinical heterogeneity, and the publication bias is analyzed through Funnel plot. Taking the incidence of lung infection as an example, the results are evenly distributed on both sides of the Funnel plot, and the publication bias has little impact on the results of the study. Conclusion: Compared with parenteral nutrition, mixed nutrition can improve the prognosis of postoperative patients with esophageal cancer and reduce the incidence of related adverse events.

First-line immunotherapy efficacy in advanced squamous non-small cell lung cancer with PD-L1 expression ≥50%: a network meta-analysis of randomized controlled trials.

Objective: The optimal first-line immunotherapy regimen for patients with PD-L1 expression ≥50% in squamous non-small cell lung cancer (Sq-NSCLC) remains uncertain. This study utilized net-work meta-analysis (NMA) to indirectly compare the efficacy of various first-line immuno-therapy regimens in this patient subset. Methods: Systematic searches were conducted across PubMed, the Cochrane Library, Web of Science, and Embase databases for randomized controlled trials reporting overall survival (OS) and progression-free survival (PFS) outcomes. The search spanned from database inception to November 3, 2023. Bayesian network meta-analysis was employed for a comprehen-sive analysis. To ensure scientific rigor and transparency, this study is registered in the Interna-tional Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42022349712. Results: The NMA encompassed 9 randomized controlled trials (RCTs), involving 2170 patients and investigating 9 distinct immunotherapy regimens. For OS, the combination of camrelizumab and chemotherapy demonstrated the highest probability (36.68%) of efficacy, fol-lowed by cemiplimab (33.86%) and atezolizumab plus chemotherapy (23.87%). Regarding PFS, the camrelizumab and chemotherapy combination had the highest probability (39.70%) of efficacy, followed by pembrolizumab (22.88%) and pembrolizumab plus chemotherapy (17.69%). Compared to chemotherapy, first-line treatment with immune checkpoint inhibitors (ICIs) in Sq-NSCLC pa-tients exhibited significant improvements in OS (HR 0.59, 95% CI 0.47-0.75) and PFS (HR 0.44, 95% CI 0.37-0.52). Conclusion: This study suggests that, for Sq-NSCLC patients with PD-L1 expression ≥50%, the first-line immunotherapy regimen of camrelizumab plus chemotherapy provides superior OS and PFS outcomes. Furthermore, ICIs demonstrate enhanced efficacy compared to chemotherapy in this patient population. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD 42022349712.