Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

Objective: Recent studies indicate that 3 morphological types of atlanto-occipital joint (AOJ) exist in the craniovertebral junction and are associated with type II basilar invagination (BI) and atlanto-occipital instability. However, the actual biomechanical effects remain unclear. This study aims to investigate biomechanical differences among AOJ types I, II, and III, and provide further evidence of atlanto-occipital instability in type II BI. Methods: Models of bilateral AOJ containing various AOJ types were created, including I-I, I-II, II-II, II-III, and III-III models, with increasing AOJ dysplasia across models. Then, 1.5 Nm torque simulated cervical motions. The range of motion (ROM), ligament and joint stress, and basion-dental interval (BDI) were analyzed. Results: The C0–1 ROM and accompanying rotational ROM increased progressively from model I-I to model III-III, with the ROM of model III-III showing increases between 27.3% and 123.8% indicating ultra-mobility and instability. In contrast, the C1–2 ROM changes were minimal. Meanwhile, the stress distribution pattern was disrupted; in particular, the C1 superior facet stress was concentrated centrally and decreased substantially across the models. The stress on the C0–1 capsule ligament decreased during cervical flexion and increased during bending and rotating loading. In addition, BDI gradually decreased across the models. Further analysis revealed that the dens showed an increase of 110.1% superiorly and 11.4% posteriorly, indicating an increased risk of spinal cord impingement. Conclusion Progressive AOJ incongruity critically disrupts supportive tissue loading, enabling incremental atlanto-occipital instability. AOJ dysplasia plays a key biomechanical role in the pathogenesis of type II BI.

Objective: Recent studies indicate that 3 morphological types of atlanto-occipital joint (AOJ) exist in the craniovertebral junction and are associated with type II basilar invagination (BI) and atlanto-occipital instability. However, the actual biomechanical effects remain unclear. This study aims to investigate biomechanical differences among AOJ types I, II, and III, and provide further evidence of atlanto-occipital instability in type II BI. Methods: Models of bilateral AOJ containing various AOJ types were created, including I-I, I-II, II-II, II-III, and III-III models, with increasing AOJ dysplasia across models. Then, 1.5 Nm torque simulated cervical motions. The range of motion (ROM), ligament and joint stress, and basion-dental interval (BDI) were analyzed. Results: The C0–1 ROM and accompanying rotational ROM increased progressively from model I-I to model III-III, with the ROM of model III-III showing increases between 27.3% and 123.8% indicating ultra-mobility and instability. In contrast, the C1–2 ROM changes were minimal. Meanwhile, the stress distribution pattern was disrupted; in particular, the C1 superior facet stress was concentrated centrally and decreased substantially across the models. The stress on the C0–1 capsule ligament decreased during cervical flexion and increased during bending and rotating loading. In addition, BDI gradually decreased across the models. Further analysis revealed that the dens showed an increase of 110.1% superiorly and 11.4% posteriorly, indicating an increased risk of spinal cord impingement. Conclusion Progressive AOJ incongruity critically disrupts supportive tissue loading, enabling incremental atlanto-occipital instability. AOJ dysplasia plays a key biomechanical role in the pathogenesis of type II BI.

Objective: Recent studies indicate that 3 morphological types of atlanto-occipital joint (AOJ) exist in the craniovertebral junction and are associated with type II basilar invagination (BI) and atlanto-occipital instability. However, the actual biomechanical effects remain unclear. This study aims to investigate biomechanical differences among AOJ types I, II, and III, and provide further evidence of atlanto-occipital instability in type II BI. Methods: Models of bilateral AOJ containing various AOJ types were created, including I-I, I-II, II-II, II-III, and III-III models, with increasing AOJ dysplasia across models. Then, 1.5 Nm torque simulated cervical motions. The range of motion (ROM), ligament and joint stress, and basion-dental interval (BDI) were analyzed. Results: The C0–1 ROM and accompanying rotational ROM increased progressively from model I-I to model III-III, with the ROM of model III-III showing increases between 27.3% and 123.8% indicating ultra-mobility and instability. In contrast, the C1–2 ROM changes were minimal. Meanwhile, the stress distribution pattern was disrupted; in particular, the C1 superior facet stress was concentrated centrally and decreased substantially across the models. The stress on the C0–1 capsule ligament decreased during cervical flexion and increased during bending and rotating loading. In addition, BDI gradually decreased across the models. Further analysis revealed that the dens showed an increase of 110.1% superiorly and 11.4% posteriorly, indicating an increased risk of spinal cord impingement. Conclusion Progressive AOJ incongruity critically disrupts supportive tissue loading, enabling incremental atlanto-occipital instability. AOJ dysplasia plays a key biomechanical role in the pathogenesis of type II BI.

Objective: Recent studies indicate that 3 morphological types of atlanto-occipital joint (AOJ) exist in the craniovertebral junction and are associated with type II basilar invagination (BI) and atlanto-occipital instability. However, the actual biomechanical effects remain unclear. This study aims to investigate biomechanical differences among AOJ types I, II, and III, and provide further evidence of atlanto-occipital instability in type II BI. Methods: Models of bilateral AOJ containing various AOJ types were created, including I-I, I-II, II-II, II-III, and III-III models, with increasing AOJ dysplasia across models. Then, 1.5 Nm torque simulated cervical motions. The range of motion (ROM), ligament and joint stress, and basion-dental interval (BDI) were analyzed. Results: The C0–1 ROM and accompanying rotational ROM increased progressively from model I-I to model III-III, with the ROM of model III-III showing increases between 27.3% and 123.8% indicating ultra-mobility and instability. In contrast, the C1–2 ROM changes were minimal. Meanwhile, the stress distribution pattern was disrupted; in particular, the C1 superior facet stress was concentrated centrally and decreased substantially across the models. The stress on the C0–1 capsule ligament decreased during cervical flexion and increased during bending and rotating loading. In addition, BDI gradually decreased across the models. Further analysis revealed that the dens showed an increase of 110.1% superiorly and 11.4% posteriorly, indicating an increased risk of spinal cord impingement. Conclusion Progressive AOJ incongruity critically disrupts supportive tissue loading, enabling incremental atlanto-occipital instability. AOJ dysplasia plays a key biomechanical role in the pathogenesis of type II BI.

Objective: Recent studies indicate that 3 morphological types of atlanto-occipital joint (AOJ) exist in the craniovertebral junction and are associated with type II basilar invagination (BI) and atlanto-occipital instability. However, the actual biomechanical effects remain unclear. This study aims to investigate biomechanical differences among AOJ types I, II, and III, and provide further evidence of atlanto-occipital instability in type II BI. Methods: Models of bilateral AOJ containing various AOJ types were created, including I-I, I-II, II-II, II-III, and III-III models, with increasing AOJ dysplasia across models. Then, 1.5 Nm torque simulated cervical motions. The range of motion (ROM), ligament and joint stress, and basion-dental interval (BDI) were analyzed. Results: The C0–1 ROM and accompanying rotational ROM increased progressively from model I-I to model III-III, with the ROM of model III-III showing increases between 27.3% and 123.8% indicating ultra-mobility and instability. In contrast, the C1–2 ROM changes were minimal. Meanwhile, the stress distribution pattern was disrupted; in particular, the C1 superior facet stress was concentrated centrally and decreased substantially across the models. The stress on the C0–1 capsule ligament decreased during cervical flexion and increased during bending and rotating loading. In addition, BDI gradually decreased across the models. Further analysis revealed that the dens showed an increase of 110.1% superiorly and 11.4% posteriorly, indicating an increased risk of spinal cord impingement. Conclusion Progressive AOJ incongruity critically disrupts supportive tissue loading, enabling incremental atlanto-occipital instability. AOJ dysplasia plays a key biomechanical role in the pathogenesis of type II BI.

Objective To observe the effect of tanshinone ⅡA on renal transforming growth factor beta 1 (TGF-β1) and nuclear factor-kappa B (NF-κB) p65 mRNA and protein expression in diabetic nephropathy (DN) rats, thus to evaluate the therapeutic effect and mechanism of tanshinone ⅡA. Methods SD rats were used as the experimental animal. DN rat model was induced with 40 mg/kg of streptozocin ( STZ) . The rats were randomized into normal group, model group, and tanshinone ⅡA ( 10 mg·kg -1·d -1, im) group. On the experimental day 30, we examined the body weight, water in-take volume, 24-hour urine protein, fasting glucose ( Glu) , serum creatinine ( Cr) , blood urea nitrogen ( BUN) , total protein ( TP) and albumin ( Alb). Renal slices after periodic acid Schiff staining ( PAS) were used for the observation of renal pathology. Semi-quantitative reverse transcription polymerase chain reaction ( RT-PCR) was used for the detection of renal TGF-β1 and NF-κB p65 mRNA expression, and Western blotting method was used for the measurement of TGF-β1 and NF-κB p65 protein expression in rats of different groups. Results Compared with the normal group, body weight was decreased, water in-take volume and 24-hour urine protein were increased, serum Glu, Cr, and BUN levels were elevated, TP and Alb levels were decreased, renal pathological damage occurred, and renal TGF-β1 and NF-κB p65 mRNA and protein expressin were promoted in the model group (P<0.05 or P<0.01). Tanshinone ⅡA group had an effect on decreasing water in-take volume, 24-hour urine protein, serum levels of Glu, Cr and Bun, increasing TP and Alb levels, relieving renal pathological damage, and reducing the protein and mRNA expression of renal TGF-β1 and NF-κB p65 ( P<0.05 or P<0.01 compared with the model group). Conclusion Tanshinone ⅡA has protective effect on kidney probably through inhibiting renal TGF-β1 and NF-κB p65 expression in DN rats.

Objective To observe the effect of human serum containing Niaoduqing Capsule(NC)on proliferation and transdifferentiation of human renal tubular epithelial cells(HK-2).Methods The in-vitro cultured HK-2 were divided into 6 groups according to the culture media: normal control group,uremic serum groups(at the concentration of 5% and 10%), NC-containing serum groups(at the concentration of 5% and 10%),and Monopril group(at the concentration of 10-6mmol/L).Cell proliferation was measured by methylene blue assay.Cell life cycle and the percentage of cells with ?-smooth muscle actin(?-SMA)expression positive in every group were evaluated by flow cytometry.Results The optical absorption value in uremic serum groups was higher than that in the normal control group(P

Objective To observe the effect of Niaodu Qing Capsule(NQC) and its separated prescriptions on renal transforming growth factor ?1(TGF-?1)mRNA expression in rats with chronic renal failure(CRF).Methods SD rat models of CRF were induced by 5/6 nephrectomy,and then the CRF rats were randomized into model group,Huangqi(Radix Astragali,1.5 g?kg-1?d-1) group,Danshen(Radix Salviae Miltiorrhizae,1 g?kg-1?d-1) group,Dahuang(Radix et Rhizoma Rhei,1 g?kg-1?d-1) group,Huangqi Danshen Dahuang(1 g?kg-1?d-1) group,NQC group(1 g?kg-1?d-1).Except the model group,the rats in other groups received gastric gavage of corresponding medicine according to the experimental design.After treatment for six weeks,the levels of blood urea nitrogen(BUN) and serum creatinine(SCr) were detected,and the expression level of renal TGF-?1 mRNA was examined by reverse transcription polymerase chain reaction(RT-PCR).Results The levels of BUN and SCr were decreased in the medicated groups(P

To explore the synergistic action of Kangshen Tablet (KT), which has the functions of nourishing kidney, invigorating spleen, eliminating stasis and turbidity, in maintenance hemodialysis for chronic renal failure (CRF).Eighty cases of CRF were randomly allocated to Group A (maintenance hemodialysis alone) and Group B (KT combined with maintenance hemodialysis).Serum creatine (SCr) and blood urea nitrogen (BUN) levels, average times of hemodialysis per week, adequacy of hemodialysis, nutrition status, cellular immune function, survival rate and serum electrolyte levels were observed.After treatment, SCr and BUN levels were decreased, average times of hemodialysis per week reduced, adequacy of hemodialysis raised, nutrition status improved, cellular immune function promoted, survival rate increased and hyperphospheremia decreased in Group B (P