Macrophage colony-stimulating factor (M-CSF or CSF-1) is known to have a broad range of actions on myeloid cells maturation, including the regulation of macrophage differentiation, proliferation and survival. Macrophages generated by M-CSF stimulus have been proposed to be alternatively activated or M2 phenotype. M-CSF is commonly overexpressed by tumors and is also known to enhance tumor growth and aggressiveness via stimulating pro-tumor activities of tumor-associated macrophages (TAMs). Currently, inhibition of CSF-1/CSF-1R interaction by therapeutic antibody to deplete TAMs and their pro-tumor functions is becoming a prevalent strategy in cancer therapy. However, its antitumor activity shows a limited single-agent effect. Therefore, macrophages in response to M-CSF interruption are pending for further investigation. To achieve this study, bone marrow derived macrophages were generated in vitro by M-CSF stimulation for 7 days and then continuously grown until day 21 in M-CSF absence. A selective pressure for cell survival was initiated after withdrawal of M-CSF. The surviving cells were more prone to M2-like phenotype, even after receiving interleukin-4 (IL-4) stimulation. The transcriptome analysis unveiled that endogenous CSF-1 level was dramatically up-regulated and numerous genes downstream to CSF-1 covering tumor necrosis factor (TNF), ras-related protein 1 (Rap1) and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway were significantly modulated, especially for proliferation, migration and adhesion. Moreover, the phenomenal increase of miR-21-5p and genes related to pro-tumor activity were observed in parallel. In summary, withholding of CSF-1/CSF-1R interaction would rather augment than suspend the M-CSF-driven pro-tumor activities of M2 macrophages in a long run.
Heat stress is among the most challenging environmental conditions affecting commercial poultry. It severely affects growth and egg production, particularly in tropical and subtropical regions. This study aimed to examine physiological responses – including triiodothyronine (T3) levels, enzymatic activity of creatine kinase (CK) and lactate dehydrogenase (LDH), respiratory rates, and cloacal temperature – to acute heat stress associated with different genotypes of the HSP70 gene and to evaluate the association of these polymorphisms with growth and egg production. Genotyping was performed by single-strand conformation polymorphism analysis. The polymorphisms identified were A258A, A258G, and G258G. Twenty 12-week old birds were randomly selected from each genotype and exposed to 40 °C ambient temperature for 1 h. Blood samples were collected at 0 and 1 h following heat stress. Respiratory rate and cloacal temperature were measured following 0, 30, and 60 min of exposure. After 1 h, the A258A genotype exhibited lower levels of CK activity and plasma T3. Neither respiratory rate nor cloacal temperature displayed a significant association with the genotypes. Body weight gain differed among the genotypes for males (F = 3.268, P = 0.041) and females (F = 14.029, P < 0.001), and the A258A genotype exhibited the greatest weight gain at 0–16 weeks of age for both genders. There were no significant differences among genotypes regarding egg weight at first egg or the number of eggs laid until 40 weeks of age. The A258A genotype displayed higher heat tolerance with no negative effects on growth performance and egg production.
This study investigates the effects of two-stage fermented feather meal-soybean meal product (TSFP) on growth performance, blood characteristics, and immunity of finishing pigs. Firstly, feather meal-soybean meal is subjected to aerobic fermentation with Bacillus subtilis var. natto N21, B. subtilis Da2 and Da15, B. amyloliquefaciens Da6, Da16 for two days, and anaerobic fermentation with B. coagulans L12 for three days. Then, the fermented product is air-dried into an end product—TSFP. Eighty hybrid pigs (Duroc x KHAPS) with equal numbers of both sexes are randomly assigned into 3% fish meal, 0%, 2.5%, or 5.0% TSFP groups with five replicates per group. Our results show that the average daily feed intake and feed conversion rate of TSFP groups are significantly better than the other groups at 0–3 weeks (p < 0.05). The 5% TSFP group significantly increased HDL-C in the blood (p < 0.05), and decreased LDL-C and blood urea nitrogen content (p < 0.05). The lipopolysaccharide (LPS) and concanavalin A (ConA) in 5% TSFP group and interferon-γ (IFN-γ) content in 2.5% and 5% TSFP groups are significantly higher than the other groups (p < 0.05). The phagocytic oxygen burst capacity and serum IgA content of the 5% TSFP group are significantly higher than those of the fishmeal group (p < 0.05). The CD3, CD4, and CD4 + CD8 + T cells subsets in 2.5% and 5% TSFP groups are significantly higher than the control group (p < 0.05). In conclusion, TSFP has a positive effect on the growth performance and immunity of finishing pigs with the best performance on 5% TSFP.
Osteoarthritis (OA) is a major public and animal health challenge with significant economic consequences. Cartilage degradation plays a critical role in the initiation and progression of degenerative joint diseases, such as OA. Mesenchymal stem cells (MSCs) have become increasingly popular in the field of cartilage regeneration due to their promising results. The objective of this preclinical study was to evaluate the regenerative effects of mesenchymal stem cells (MSCs) in the repair of knee cartilage defects using a porcine model. Seven healthy LYD breed white pigs, aged 9–10 weeks and weighing approximately 20 ± 3 kg, were used in the experimental protocol. Full-thickness defects measuring 8 mm in diameter and 5 mm in depth were induced in the lateral femoral condyle of the posterior limbs in both knee joints using a sterile puncture technique while the knee was maximally flexed. Following a 1-week induction phase, the pig treatment groups received a 0.3 million/kg MSC transplant into the damaged knee region, while the placebo group received a control solution as a treatment. Magnetic resonance imaging (MRI), computerized tomography (CT), visual macroscopic examination, histological analysis, and cytokine concentration analysis were used to assess cartilage regeneration. The findings revealed that human adipose-derived mesenchymal stem cells (hADSCs) were more effective in repairing cartilage than pig umbilical cord-derived mesenchymal stem cells (pUCMSCs). These results suggest that MSC-based treatments hold promise as a treatment option for cartilage repair, which aid in the treatment of OA. However, further studies with larger sample sizes and longer follow-up periods are required to fully demonstrate the safety and efficacy of these therapies in both animals and humans.
Cryptocaryone (CPC) was previously reported as preferential for killing natural products in oral cancer cells. However, its radiosensitizing potential combined with ultraviolet C (UVC) cell killing of oral cancer cells remains unclear. This study evaluates the combined anti-proliferation effect and clarifies the mechanism of combined UVC/CPC effects on oral cancer cells. UVC/CPC shows higher anti-proliferation than individual and control treatments in a low cytotoxic environment on normal oral cells. Mechanistically, combined UVC/CPC generates high levels of reactive oxygen species and induces mitochondrial dysfunction by generating mitochondrial superoxide, increasing mitochondrial mass and causing the potential destruction of the mitochondrial membrane compared to individual treatments. Moreover, combined UVC/CPC causes higher G2/M arrest and triggers apoptosis, with greater evidence of cell cycle disturbance, annexin V, pancaspase, caspases 3/7 expression or activity in oral cancer cells than individual treatments. Western blotting further indicates that UVC/CPC induces overexpression for cleaved types of poly (ADP-ribose) polymerase and caspase 3 more than individual treatments. Additionally, UVC/CPC highly induces γH2AX and 8-hydroxy-2’-deoxyguanosine adducts as DNA damage in oral cancer cells. Taken together, CPC shows a radiosensitizing anti-proliferation effect on UVC irradiated oral cancer cells with combined effects through oxidative stress, apoptosis and DNA damage.
Taiwan’s subtropical climate poses substantial heat stress challenges to poultry production. This study compared four red-feathered rooster lines (n = 10 per line, BB homozygous HSP70 genotype)—three commercially bred lines (F, T, K) selected for maximum body weight, and one native trial line (TLRI-09) developed through marker-assisted selection targeting the HSP70 BB genotype—during a one-hour acute heat challenge at 42 °C. A pre-specified statistical decision tree was applied: normality was assessed by the Shapiro–Wilk test for each group’s change score (Δ = post − pre); one-way ANOVA with Tukey’s HSD was used when all groups were normally distributed; Kruskal–Wallis with Dunn’s post hoc test (Bonferroni correction) was used otherwise. Within-group pre-to-post changes were assessed by paired t-test. TLRI-09 showed a substantially lower body weight (909 ± 102 g vs. 2039–2226 g) and zero mortality, whereas each commercial line experienced one death (10%). Cloacal temperatures in F, T, and K groups exceeded the thermometer’s upper limit (>44 °C) within one hour; TLRI-09 reached only 42.8 ± 0.1 °C. Respiratory rate increment was highest in TLRI-09 (Δ = 82.0 ± 8.4 breaths/min) and differed significantly among lines (p < 0.001). Plasma T3 change differed among lines (p = 0.006); post hoc analysis identified a significant K vs. T contrast only (p = 0.019). These results indicate that, despite sharing the same HSP70 genotype, breeding objective is an important determinant of acute thermal resilience—an observation that warrants further validation under chronic and commercial production conditions.