The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Objective To explore the guiding significance of preoperative 3D reconstruction for pulmonary nodule location and thoracoscopic surgical method selection in lung cancer patients. Methods The clinical data of the patients with preoperative 3D reconstruction in our China-Japan Friendship Hospital between January and November 2023 were retrospectively analyzed. Preoperative surgical planning was performed using 3D reconstruction. Different surgical procedure, including wedge resection, segmentectomy, lobectomy, or combined surgical procedure were performed based on tumor location, size and distance from the pleura. Results A total of 115 patients were included with 45 males and 70 females, at an average age of 25-84 (58.29±11.36) years and successfully completed the operation. Fifty-five (47.8%) patients' nodule diameter was tangent cross-section, among whom twenty-five (21.7%) patients of nodules crossed sections. There were 21 patients of wedge resection in the outer 1/3 nodules of CT, which had shorter operation time and less cost (P<0.001) and less intraoperative bleeding (P=0.019). For the crossing sections or edge crossing sections nodules of the middle and inner of CT, 6 patients were of simple pulmonary segmentectomy, 8 patients of combined with sub-segmentectomy, 7 patients of combined segmentectomy, 5 patients of lobectomy, and 3 patients of wedge resection. Conclusion The proportion of cross-segment pulmonary nodules is relatively high. For the outer 1/3 nodules of CT, compared with pulmonary segmental resection combined with adjacent lung tissue resection, wedge resection can also ensure sufficient surgical margin, and the middle and inner 1/3 nodules of CT need to be combined with adjacent pulmonary tissue resection to ensure the surgical edge.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
Humans ; Bone Remodeling ; Cell Differentiation ; Osteogenesis ; Semaphorin-3A/pharmacology* ; Trigeminal Ganglion/metabolism*

Objective·To reveal the direction,efficiency,and mechanical load of single tooth displacement with clear aligners for expansion treatment during the transitional dentition period with the aid of finite element analysis.Additionally,overcorrection and torque compensation systems were designed to address insufficient expansion efficiency and buccal inclination of posterior teeth.Methods·One volunteer in mixed dentition period was included to construct a three dimentional cranio-maxillary complex model and an invisible orthodontic system,simulating the buccal displacement(load 1?4:0.200,0.275,0.300,0.325 mm,respectively)and root buccal torque(load 1:buccal displacement load 0.200 mm,root buccal torque 0°;load 5:buccal displacement load 0.275 mm,root buccal torque 1.0°;load 6:buccal displacement load 0.300 mm,root buccal torque 1.3° and load 7:buccal displacement load 0.325mm,root buccal torque 1.8°)on the maxillary deciduous teeth to the first permanent molar with a non bracket invisible orthodontic appliance.Through finite element analysis,the tooth displacement and equivalent stress distribution of the periodontal membrane can be calculated.Results·Expansion treatment with clear aligners in the transitional dentition phase primarily revealed the effect of buccal expansion of teeth;different teeth achieved different levels of expansion rate.At a set expansion amount of 0.200 mm per side,expansion efficiency in the maxillary first permanent molar was 51.86%,second primary molar 68.76%,first primary molar 73.48%,and primary cuspid 84.17%.By designing over-correction(0.275,0.300,0.325 mm),the results showed significant enhancement in expansion effect.When overcorrection length reached 150%(0.300 mm),expansion efficiency at the maxillary first permanent molar,second primary molar,first primary molar,and primary cuspid were 75.16%,99.96%,107.35%,and 122.37%,respectively.The expansion efficiency of maxillary second primary molar,first primary molar,and primary cuspid was close to 100.00%.The overcorrection design exacerbated the dental effects of expansion,intensifying the tendency for teeth to tilt toward the cheek side,leading to side effects such as buccal inclination and drooping of the palatal cusps.When the overcorrection amount for expansion reached 150%,the crown-root displacement in the upper first permanent molar,second primary molar,first primary molar,and primary cuspid were-0.109,-0.134,-0.132,and-0.298 mm,respectively.Applying specific torque compensation for different tooth positions can combat the buccal inclination of posterior teeth.At an overcorrection length of 150%(0.300 mm)with an added 1.3° root buccal torque,expansion efficiency was 56.15%,73.88%,79.49%,and 87.80%,respectively.While the crown-root displacement differences reduced to-0.081,-0.097,-0.095,and-0.208 mm.Conclusion·When using clear aligners for expansion treatment during a transitional dentition period,side effects such as buccal inclination of posterior teeth exist.Furthermore,various teeth realize differing levels of expansion efficiency,necessitating the design of unique adjustment strategies according to different tooth positions.Overcorrection can improve expansion efficiency but needs to be coordinated with root buccal torque for the whole tooth to move buccally.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.