Ferroptosis represents a distinct form of cell death that is not associated with necrosis, autophagy, apoptosis, or pyroptosis. It is characterised by intracellular iron-dependent lipid peroxidation. The current literature indicates that a number of botanical drugs and isolated metabolites can modulate ferroptosis, thereby exerting inhibitory effects on lung cancer cells or animal models. The aim of this review is to elucidate the mechanisms through which botanical drugs and isolated metabolites regulate ferroptosis in the context of lung cancer, thereby providing potential insights into lung cancer treatment. It is crucial to highlight that these preclinical findings should not be interpreted as evidence that these treatments can be immediately translated into clinical applications. In the future, we will continue to study the pharmacology, pharmacokinetics and toxicology of these drugs, as well as evaluating their efficacy and safety in clinical trials, with the aim of providing new approaches to the development of new agents for the treatment of lung cancer.

OBJECTIVE: The aim of this experimental in vivo pilot study was to evaluate the effect of the local delivery of pamidronate within a collagen membrane on the changes in the buccal soft and hard tissue dimensions at the time of immediate implant placement and whether this effect was influenced by the placement of bone substitutes.
METHODS: In six beagle dogs, the distal roots of the third and fourth premolars were extracted, and immediate implants were placed. Treatment groups were randomly allocated to each socket: (i) covering the buccal bone with pamidronate-soaked collagen membrane (BP group), (ii) filling the gap defect with synthetic bone substitute (BS group), (iii) filling the gap defect with synthetic bone substitute and covering the buccal bone with pamidronate soaked collagen membrane (BP/BS group), (iv) no treatment (control group). Intraoral scanning was performed immediately after the surgery and at 20 weeks. Histomorphometric and micro-computed tomography (CT) outcomes were evaluated at 20 weeks.
RESULTS: The micro CT analysis demonstrated that the BP group showed no apparent difference in vertical bone level with residual mesial root area, while control group showed significant buccal bone resorption at the implant site. The histomorphometric analysis demonstrated that the vertical bone level of buccal plate was significantly differed between the BP and control group (0.34 ± 0.93 and 1.27 ± 0.56 mm, respectively; p = .041). There was no statistically significant difference in the horizontal ridge width (HRW 1, 2, 3) among the groups. Also, the thickness, height and buccal contours of the soft tissue did not reveal significant changes among the groups.
CONCLUSIONS: The local delivery of pamidronate to the outer surface of the buccal wall at the time of immediate implant placement effectively limits buccal bone resorption. The results from the present investigation should be interpreted with caution, as well as its clinical translatability. Further investigation is needed to understand the pamidronate binding and releasing kinetic, as well as the ideal carrier of this drug for its topical application.

OBJECTIVE: To investigate the local, downstream, and systemic effects of two different paclitaxel-coated balloons.
METHODS: Preclinical study in healthy peripheral arteries of a swine model, with randomized allocation of the distribution of the devices: the test paclitaxel-coated balloon (PCB) (Luminor®), a control PCB (IN.PACT®), and a plain angioplasty balloon (Oceanus®), considering single (1×) and overlapping (3×) doses with simple blind histologic analysis.
METHODS: Twenty animals underwent balloon angioplasty at 1× or 3× doses in the external and internal branches of both femoral arteries and were followed-up for 28 days. Post-procedural and follow-up angiography were carried out. Comprehensive necropsy and histology were used to evaluate the local, downstream and systemic effects.
RESULTS: Angioplasty was successfully carried out in all animals. Significant protocol deviations appeared in three arteries (treated with Oceanus®) without clinical relevance. Those samples were excluded from the analysis. All the animals survived the follow-up period without major clinical issues. Local signs of drug toxicity were less marked with Luminor® than IN.PACT® at 1× dose, including endothelial loss (p=0.0828), intima/media inflammation (p=0.0004), transmural medial smooth muscle cell (SMC) loss (p=0.0016), wall thickness loss (p=0.0141), presence of fibrin in the vascular wall (p=0.0054), and adventitial inflammation (p=0.0080). A similar pattern was observed at the 3× dose for endothelial loss (p=0.0011), intima/media inflammation (p< 0.0001), circumferential SMC loss (p=0.0004), medial SMC replacement with proteoglycans (p=0.0014), fibrin (p=0.0034), and collagen content (p=0.0205). Downstream vascular histologic changes were mild although more prevalent in the IN.PACT® 3× group (p=0.006). No systemic effects of toxicity were detected in any of the samples analyzed.
CONCLUSIONS: Luminor® showed better healing pattern (lower inflammation, and endothelial and muscular loss) than IN.PACT® balloon. The effect was evident at single and triple doses. The prevalence of downstream lesions, albeit low, was higher with the triple dose of IN.PACT® compared with Luminor®.

BACKGROUND: Pericardial fluid (PF) contains cells, proteins, and inflammatory mediators, such as cytokines, chemokines, growth factors, and matrix metalloproteinases. To date, we lack an adequate understanding of the inflammatory response that acute injury elicits in the pericardial space.
OBJECTIVE: To characterize the inflammatory profile in the pericardial space acutely after ischemia/reperfusion.
METHODS: Pigs were used to establish a percutaneous ischemia/reperfusion injury model. PF was removed from pigs at different time points postanesthesia or postischemia/reperfusion. Flow cytometry was used to characterize the immune cell composition of PF, while multiplex analysis was performed on the acellular portion of PF to determine the concentration of inflammatory mediators. There was a minimum of 3 pigs per group.
RESULTS: While native PF mainly comprises macrophages, we show that neutrophils are the predominant inflammatory cell type in the pericardial space after injury. The combination of acute ischemia/reperfusion (IR) and repeatedly accessing the pericardial space significantly increases the concentration of interleukin-1 beta (IL-1β) and interleukin-1 receptor antagonist (IL-1ra). IR significantly increases the pericardial concentration of TGFβ1 but not TGFβ2. We observed that repeated manipulation of the pericardial space can also drive a robust pro-inflammatory response, resulting in a significant increase in immune cells and the accumulation of potent inflammatory mediators in the pericardial space.
CONCLUSIONS: In the present study, we show that both IR and surgical manipulation can drive robust inflammatory processes in the pericardial space, consisting of an increase in inflammatory cytokines and alteration in the number and composition of immune cells.

UNASSIGNED: Wound healing has always been a serious issue for doctors and primary health care systems. In addition, adipose stem cell-derived exosomes have been proven to play a positive and effective role in tissue repair and regeneration. A systematic review of these preclinical studies was performed to assess the efficacy of adipose stem cell-derived exosomes (ADSC-Exos) in treating wounds. This article aimed to study the effectiveness of ADSC-Exos for the treatment of animal skin wounds and includes a meta-analysis of exosomes from general wounds and diabetic ulcer wounds in in vitro models of animals to provide a theoretical basis for clinical translation.
UNASSIGNED: A total of 19 studies with 356 animals were identified by searching the PubMed, Cochrane, MEDLINE Complete, Web of Science, CNKI and Wanfang databases from inception to 15 November 2022. No language or time restrictions were applied. Stata17 was used for all the data analyses.
UNASSIGNED: The meta-analysis showed that ADSC-Exo therapy significantly improved the wound healing rate in the control group, except in the diabetes group on day 7. Day 7 of general wounds [standard mean difference (SMD) 2.87, 95% confidence interval (CI) 1.91-3.83)] and day 14 (SMD 2.89, 95%CI 1.47-4.30). Day 14 (SMD 3.43, 95%CI 1.28-5.58) of diabetic wounds. Other outcomes, such as blood vessel density, collagen deposition and wound re-epithelization, improved with the administration of ADSC-Exos.
UNASSIGNED: A meta-analysis showed that ADSC-Exo therapy applied to general and diabetic wounds can promote neovascularization, improve epithelization and collagen fiber deposition, promote healing, and reduce scar formation. ADSC-Exos have broad potential in preclinical research and clinical fields.

The hinotori™ Surgical Robot System (hinotori™, Medicaroid, Kobe, Japan) is increasingly being utilized primarily in urology and adult surgery; however, data on its application in pediatric surgery are lacking. This preclinical study aimed to evaluate the limitations of this system for accurate suturing in small cavities designed for pediatric and neonatal applications. Two trained operators performed simple ligature sutures (easy task [ET]) and hepaticojejunostomy sutures (difficult task [DT]) within five differently sized boxes, ranging from 5123 to 125 mL. The suture time, number of internal and external instrument/instrument collisions, instrument/box collisions, and suture accuracy were evaluated. The suture accuracy was assessed using the A-Lap Mini endoscopic surgery skill assessment system. As a result, an increase in the number of collisions and extended suturing times were observed in boxes with volumes smaller than 215 mL. Despite these variations, there were no significant differences between the boxes, and all tasks were precisely performed in all boxes (p = 0.10 for the ET and p = 1.00 for the DT). These findings demonstrate the capability of the hinotori™ system to perform precise suturing techniques within tightly confined simulated neonatal cavities as small as 125 mL. To advance the integration of pediatric robotic surgery utilizing the hinotori™ system, additional trials comparing it with conventional laparoscopic and thoracoscopic techniques using pediatric and animal models are necessary to assess its clinical safety and applicability.

Proton magnetic resonance spectroscopic imaging (1H-MRSI) is a powerful tool that enables the multidimensional non-invasive mapping of the neurochemical profile at high resolution over the entire brain. The constant demand for higher spatial resolution in 1H-MRSI has led to increased interest in post-processing-based denoising methods aimed at reducing noise variance. The aim of the present study was to implement two noise-reduction techniques, Marchenko-Pastur principal component analysis (MP-PCA) based denoising and low-rank total generalized variation (LR-TGV) reconstruction, and to test their potential with and impact on preclinical 14.1 T fast in vivo 1H-FID-MRSI datasets. Since there is no known ground truth for in vivo metabolite maps, additional evaluations of the performance of both noise-reduction strategies were conducted using Monte Carlo simulations. Results showed that both denoising techniques increased the apparent signal-to-noise ratio (SNR) while preserving noise properties in each spectrum for both in vivo and Monte Carlo datasets. Relative metabolite concentrations were not significantly altered by either method and brain regional differences were preserved in both synthetic and in vivo datasets. Increased precision of metabolite estimates was observed for the two methods, with inconsistencies noted for lower-concentration metabolites. Our study provided a framework for how to evaluate the performance of MP-PCA and LR-TGV methods for preclinical 1H-FID MRSI data at 14.1 T. While gains in apparent SNR and precision were observed, concentration estimations ought to be treated with care, especially for low-concentration metabolites.

The objective of the study is to investigate the safety, feasibility, and degradation profile of a novel Mg alloy-based bioresorbable coronary scaffold (JFK-PRODUCT BRS) with thin struts (110 μm). Polymer- or Mg alloy-based BRSs have not replaced nondegradable metal stents because of the higher prevalence of scaffold thrombosis and restenosis in clinical practice; these poor clinical outcomes were due to inadequate scaffold designs, including thick struts (more than 150 μm) and their inappropriate degradation processes. Fourteen healthy pigs received 17 JFK-PRODUCT BRSs in the coronary arteries and were sacrificed at 1, 6, 12, 18, and 26 months after implantation. Angiography, optical coherence tomography, microfocus X-ray computed tomography (µCT), scanning electron microscopy with energy-dispersive X-ray spectrometry (SEM-EDX), and histopathological evaluation were performed. The JFK-PRODUCT had a median percent late recoil of 11.28% at 1 month. The µCT observation confirmed that scaffold discontinuity reached 64.8% at 12 months with increased scaffold inner area thereafter, suggesting artery positive remodeling. The inflammation was mild, peaked at 18 months, and decreased thereafter. The SEM-EDX analysis demonstrated gradual degradation of the scaffold with formation of inorganic deposits, presumed to be calcium phosphates. It also revealed the disappearance of calcium phosphates at 26 months, achieving almost complete replacement of the scaffold by biocomponents. The current study demonstrated the safety and feasibility of JFK-PRODUCT with a lower acute recoil rate despite its thin struts. The scaffolds were almost completely disappeared at 26 months after implantation.

Over 4% of the global population is estimated to live with autoimmune disease, necessitating immunosuppressive treatment that is often chronic, not curative, and carries associated risks. B cells have emerged as key players in disease pathogenesis, as evidenced by partial responsiveness to B cell depletion by antibody-based therapies. However, these treatments often have transient effects due to incomplete depletion of tissue-resident B cells. Chimeric antigen receptor (CAR) T cells targeting B cells have demonstrated efficacy in refractory systemic lupus erythematosus. To this end, we developed an anti-CD19 CAR T cell product candidate, CABA-201, containing a clinically evaluated fully human CD19 binder (IC78) with a 4-1BB costimulatory domain and CD3 zeta stimulation domain for treatment refractory autoimmune disease. Here, we demonstrate specific cytotoxic activity of CABA-201 against CD19+ Nalm6 cells with no off-target effects on primary human cells. Novel examination of CABA-201 generated from primary T cells from multiple patients with autoimmune disease displayed robust CAR surface expression and effective elimination of the intended target autologous CD19+ B cells in vitro. Together, these findings support the tolerability and activity of CABA-201 for clinical development in patients with autoimmune disease.

Obesity represents a significant health challenge, intricately linked to conditions such as type II diabetes, metabolic syndrome, and hepatic steatosis. Several existing obesity treatments exhibit limited efficacy, undesirable side effects or a limited capability to maintain therapeutics effects in the long-term. Recently, modulation Coenzyme Q (CoQ) metabolism has emerged as a promising target for treatment of metabolic syndrome. This potential intervention could involve the modulation of endogenous CoQ biosynthesis by the use of analogs of the precursor of its biosynthesis, such as β-resorcylic acid (β-RA). Here, we show that oral supplementation with β-RA, incorporated into the diet of diet-induced obese (DIO) mice, leads to substantial weight loss. The anti-obesity effects of β-RA are partially elucidated through the normalization of mitochondrial CoQ metabolism in white adipose tissue (WAT). Additionally, we identify an HFN4α/LXR-dependent transcriptomic activation of the hepatic lipid metabolism that contributes to the anti-obesity effects of β-RA. Consequently, β-RA mitigates WAT hypertrophy, prevents hepatic steatosis, counteracts metabolic abnormalities in WAT and liver, and enhances glucose homeostasis by reducing the insulin/glucagon ratio and plasma levels of gastric inhibitory peptide (GIP). Moreover, pharmacokinetic evaluation of β-RA supports its translational potential. Thus, β-RA emerges as an efficient, safe, and translatable therapeutic option for the treatment and/or prevention of obesity, metabolic dysfunction-associated steatotic liver disease (MASLD).