Although post-tuberculosis lung disease poses a substantial threat to individuals who have recovered from pulmonary tuberculosis, data showing objective functional impairment in such people are scarce. We did a systematic review and meta-analysis to estimate respiratory impairment after pulmonary tuberculosis disease and examine differences in ventilatory defects. We systematically searched Embase, MEDLINE, and CINAHL from Jan 1, 2000, to Dec 13, 2024. We included any study design with data on lung function tests in individuals with a previous diagnosis of pulmonary tuberculosis versus healthy controls. Outcomes extracted from eligible studies included forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), FEV₁ as a percentage of the predicted value (FEV₁%), FVC as a percentage of the predicted value (FVC%), and FEV₁/FVC ratio. Pre-bronchodilator values were preferentially selected. Random effects mean difference models were used when possible and standardised mean difference where it was necessary to standardise to a single scale (ie, FEV₁%, FVC%, and FEV₁/FVC ratio). Between-study heterogeneity was estimated with I². This study was prospectively registered with PROSPERO (CRD42021248838). Of the 5594 publications found, data from 19 studies were included for meta-analyses, reporting on 75 960 individuals of whom 7447 had past pulmonary tuberculosis. All studies reporting absolute values, using various levels of adjustment or standardisation, showed that previous pulmonary tuberculosis had a negative effect across all spirometric values: FEV₁ -0·41 L (95% CI -0·51 to -0·32, I²=90·4%), FVC -0·25 L (-0·33 to -0·17, I²=80·6%), and FEV₁/FVC ratio -0·37 (-0·54 to -0·19, I²=92·0%). In those studies, using reference values to derive FEV₁% and FVC %, prior pulmonary tuberculosis had a pooled standardised mean difference of -0·44 (-0·60 to -0·28, I²=95·6%) and -0·33 (-0·54 to -0·13, I²=91·3%), respectively, compared with controls. People who recover from pulmonary tuberculosis have significantly decreased lung function compared with controls, with FEV₁ more affected than FVC, giving a mixed obstructive and restrictive picture with predominantly airflow obstruction. Breathing Matters.

Surgical flaps are basic tools in reconstructive surgery. Their use may be limited by ischemia and necrosis. Few therapies address or prevent them. Genetic therapy could improve flap outcomes, but primary studies in this field present conflicting results. This systematic review and meta-analysis aimed to appraise the efficacy of external gene delivery to the flap for its survival in preclinical models. This review was registered with PROSPERO (CRD42022359982). PubMed, Embase, Web of Science, and Scopus were searched to identify studies using animal models reporting flap survival outcomes following any genetic modifications. Random-effects meta-analysis was used to calculate mean differences in flap survival with accompanying 95% CI. The risk of bias was assessed using the SYRCLE tool. Subgroup and sensitivity analyses were performed to ascertain the robustness of primary analyses, and the evidence was assessed using the GRADE approach. The initial search yielded 690 articles; 51 were eventually included, 36 of which with 1576 rats were meta-analyzed. VEGF gene delivery to different flap types significantly improved flap survival area by 15.66% (95% CI 11.80–19.52). Other interventions had smaller or less precise effects: PDGF—13.44% (95% CI 3.53–23.35); VEGF + FGF—8.64% (95% CI 6.94–10.34); HGF—5.61% (95% CI 0.43–10.78); FGF 3.84% (95% CI 1.13–6.55). Despite considerable heterogeneity, moderate risk of bias, and low quality of evidence, the efficacy of VEGF gene therapy remained significant in all sensitivity analyses. Preclinical data indicate that gene therapy is effective for increasing flap survival, but further animal studies are required for successful clinical translation.

Peripheral nerve injuries (PNIs) remain a significant clinical problem, producing permanent motor-sensory deficits and diminishing patient's quality of life. Neurotrophic growth factors, a family of biomolecules, support neuronal survival and regeneration. Among them, Brain-Derived Neurotrophic Factor (BDNF) emerged as a key modulator of neurogenesis and neuroregeneration within the peripheral nervous system. This systematic review evaluates and summarises animal-based evidence on BDNF-based therapies used in peripheral nerve injury (PNI). A literature search in PubMed, EMBASE, Scopus, and Web of Science with the latest results from 10th of October 2024 to identify animal-based studies evaluating the effects of BDNF-based therapies used in PNI. Of 785 records, 40 articles met the inclusion criteria, encompassing 1887 rats and 430 mice or rabbits across various injury models. Gathered studies heterogenicity precluded meta-analysis, but most reports showed superior axonal regeneration, myelination, and functional recovery in BDNF-based therapies compared to control groups. The benefits were most significant with multimodal strategies, including multiple neurotrophins and stem cells. Combined therapies involving multiple neurotrophic growth factors, BDNF, and stem cell therapies showed the most significant improvement in functional outcomes and histological parameters of injured nerves. These results suggest that BDNF-based therapies hold promise for effective PNI treatment. GLOSSARY.

The objective of this study was to investigate if delivering multiple doses of N-acetylcysteine (NAC) post-surgery in addition to pre-incisional administration significantly impacts the wound healing process in a rat model. Full-thickness skin incisions were carried out on the dorsum of 24 Sprague-Dawley rats in six locations. Fifteen minutes prior to the incision, half of the sites were treated with a control solution, with the wounds on the contralateral side treated with solutions containing 0.015%, 0.03% and 0.045% of NAC. In the case of the NAC treated group, further injections were given every 8 h for three days. On days 3, 7, 14 and 60 post-op, rats were sacrificed to gather material for the histological analysis, which included histomorphometry, collagen fiber organization analysis, immunohistochemistry and Abramov scale scoring. It was determined that scars treated with 0.015% NAC had significantly lower reepithelization than the control at day 60 post-op (p = 0.0018). Scars treated with 0.045% NAC had a significantly lower collagen fiber variance compared to 0.015% NAC at day 14 post-op (p = 0.02 and p = 0.04) and a lower mean scar width than the control at day 60 post-op (p = 0.0354 and p = 0.0224). No significant differences in the recruitment of immune cells and histological parameters were found. The results point to a limited efficacy of multiple NAC injections post-surgery in wound healing.

Surgical flaps are rudimentary tools in reconstructive surgery, especially following extensive solid tumour resections. They cover skin and soft tissue defects but are prone to ischaemia and necrosis. Since their primary aim is reconstruction, they rarely exhibit a therapeutic activity against the treated disease. Attempts have been made to develop a new therapeutic strategy—biologic brachytherapy, which uses genetically engineered surgical flaps as a drug delivery vehicle, allowing the flap tissue to act as a “biologic pump”. This systematic review summarizes the preclinical evidence on using genetically modified surgical flaps. A literature search was conducted in PubMed, EMBASE, Scopus and Web of Science. The initial literature search yielded 714 papers, and, eventually, seventy-seven studies were included in qualitative analysis. The results show that genetic enhancement of flaps has been used as a local or systemic therapy for numerous disease models. Frequently, it has been used to increase flap survival and limit ischaemia or promote flap survival in a non-ischemic context, with some studies focusing on optimizing the technique of such gene therapy. The results show that genetically modified flaps can be successfully used in a variety of contexts, but we need more studies to implement this research into specific clinical scenarios.

Background: Breast cancer (BC) is highly heterogeneous, with varying molecular characteristics, such as reliance on autophagy. Autophagy is a critical cellular degradation process that helps cells survive under stress, but its regulation can be influenced by altered microRNA (miRNA) expression. Studying miRNA changes during starvation-induced autophagy in both mammary epithelial cells and BC cells could reveal potential molecular therapy targets. Methods: Rat mammary gland healthy epithelial and cancer cells were subjected to starvation, and differences in proliferation, migration, invasion, autophagy, and expression of autophagy-associated miRNAs were determined. Afterward, we assessed the effects of miR-218-5p modulation on the aforementioned processes. Results: Starvation-induced autophagy reduced the proliferation of all cells and increased the invasive and migratory capacity of cancer cells (p ≤ 0.05). We identified a miRNA signature related to starvation, comprising twenty-seven miRNAs. One miRNA had a significantly elevated baseline expression, while another six, including miR-218-5p, had a significantly lower basal expression in cancer cells compared to healthy cells (p ≤ 0.05). However, starvation caused significant miRNA expression changes, with miR-218-5p being upregulated specifically in cancer cells (p = 0.20–0.01). Functional studies on the role of miR-218-5p show that its inhibition decreases migration and leads to autophagosome accumulation. The study of miR-218-5p molecular targets has shown that its inhibition of sorting nexin 18 (SNX18) may act as an important regulator of the starvation-induced response in cancer cells. Conclusions: The baseline expression of miRNA related to starvation and autophagy differs between rat mammary gland cancer and healthy cells. The response to starvation also varies between cancer cells and normal cells. Starvation induces BC-specific miRNA dysregulation, affecting particularly miR-218-5p, which acts via SNX18, promoting the cancer cells’ survival.