Tuftsin-tailored fusion protein inhibits the growth of circulating gastric tumor cells associated with macrophage phagocytosis.

Circulating tumor cells (CTCs) are a major cause of tumor metastasis and resistance to anticancer therapies. To date, no effective low-toxicity chemotherapeutic agents or antibodies have exhibited significant clinical activity against CTCs. Macrophages are important mediators of antitumor immunity. Tuftsin (TF), a tetrapeptide located at residues 289-292 of the CH2 domain of the Fc region of the IgG heavy chain, binds to Nrp-1, a receptor on the surface of macrophages that promotes phagocytosis and induces nonspecific activation of the immune system against tumors. Lidamycin (LDM) is an antitumor chemotherapy agent that is strongly cytotoxic to tumors and can dissociate into an apoprotein (LDP) and active enediyne (AE) in vitro. We previously constructed the fusion protein LDP-TF through genetic engineering and inserted the chromophore AE to produce LDM-TF, which can target macrophages to promote their phagocytic and cytotoxic activity against tumor cells. Preliminary experiments confirmed the anti-tumor activity of LDM-TFs. In this study, we found that LDM-TF effectively inhibited the growth of CTCs of gastric cancer origin and enhanced macrophage phagocytosis both in vivo and in vitro. Tumor cell expression of CD47, which helps to evade phagocytosis by macrophages, was substantially downregulated by LDM-TF. Notably, our in vitro experiments demonstrated that the combination of LDM-TF and anti-CD47 antibodies promoted phagocytosis more than either component alone. Our findings demonstrate the significant inhibitory effect of LDM-TF on the growth of CTCs of gastric cancer origin and suggest that the combination of LDM-TF and anti-CD47 antibodies may exhibit synergistic effects, thereby providing a new option for the clinical treatment of patients with advanced tumors that have metastasized.

Efficacy of Fuyuan Xingshen Decoction Combined with Butylphthalide Sodium Chloride Injection in the Treatment of Acute Cerebral Infarction and Its Effect on Hemodynamics.

Objective: This study aims to determine the curative effect of Fuyuan Xingshen Decoction combined with butylphthalide sodium chloride injection in acute cerebral infarction (ACI) treatment and its effect on hemodynamics. Methods: In our hospital, a total of 84 ACI patients from May 2020 to February 2022 were randomly divided into two groups: observation and control (n = 42 each). Fuyuan Xingshen Decoction in combination with butylphthalide sodium chloride injection was provided to the observation group, while the control group received butylphthalide sodium chloride injection alone. Both groups' clinical efficacy was observed. Before and after treatment, the neurological function of the two groups was evaluated using the National Institutes of Health Stroke Scale (NIHSS), while the daily living ability of both groups was determined using the Barthel index rating scale. Both groups were investigated for their cognitive function, before and after treatment, by using the Mini-Cog scale and Montreal Cognitive Assessment (MoCA) scale. The pulsatility index (PI), peak velocity (Vp), and mean velocity (Vm) of intracranial arteries were measured by transcranial Doppler ultrasonography before and after treatment. The levels of ubiquitin carboxy-terminal hydrolase-1 (UCH-L1), Fibulin-5, and visinin-like protein-1 (VILIP-1) in serum and the expression levels of miR-34c, miR-25, and miR-182 in peripheral blood of the two groups were compared. Both groups were observed for the incidence of adverse reactions. Results: Compared with the control (71.43%), the observation group exhibited a significantly higher effective rate of around 90.48%. In the observation group, the improvement in NIHSS, Barthel index, Mini-cog, and MoCA scores; hemodynamic indexes including Vp, PI, and Vm; serum UCH-L1, Fibulin-5, and VILIP-1 levels; and the miR-34c, miR-25, and miR-182 expression levels in peripheral blood was better than the control group, with significant difference (all P < 0.05). The incidence of adverse reactions between the groups demonstrated no significant differences (P > 0.05). Conclusions: Fuyuan Xingshen Decoction combined with butylphthalide sodium chloride injection can effectively improve patients' daily living ability, neurological function, cognitive function, and cerebral hemodynamics in the treatment of ACI, with good effect and safety.

Simvastatin ameliorates cognitive impairments via inhibition of oxidative stress­induced apoptosis of hippocampal cells through the ERK/AKT signaling pathway in a rat model of senile dementia.

Senile dementia is a degenerative disease of the nervous system associated with cognitive impairments, memory disorders, executive dysfunctions, cognitive decline and dementia. Previous reports suggested that simvastatin presents ameliorative effects in the progression of senile dementia. However, the mechanism underlying simvastatin­mediated improvements of cognitive competence during the progression of senile dementia remains to be elucidated. In the present study, a potential mechanism underlying simvastatin activity in hippocampal cells, was investigated. Results of the present study demonstrated that simvastatin significantly improved cognitive impairments, memory competence, amyloid plaques, loss of neurons and synapses, neurofibrillary tangles and oxidative damage in experimental rats. Results of the present study demonstrated that administration of simvastatin regulates superoxide dismutase, reactive oxygen species, catalase and glutathione in oxidative stress processes in hippocampal cells. Apoptosis of hippocampal cells was suppressed by simvastatin treatment in rats with senile dementia. Notably, the administration of simvastatin inhibited activating transcription factor­6­mediated extracellular signal­regulated kinase/AKT serine/threonine kinase (ERK/AKT) signaling pathway in hippocampal cells. Taken together, the preclinical results of the present study indicate that simvastatin is efficient in preventing memory lapse and inhibiting apoptosis of hippocampal cells via the ERK/AKT signaling pathway, which may in the future improve cognitive decline and dementia in patients.

[Numerical simulation of the multi-dimensional phase-change problem in cryosurgery].

The phase change process in cryosurgery is simulated here with finite element scheme. The calculated results are consistent with experimental results. The compared results confirm the feasibility of the enthalpy model and finite element simulation method. And the successive Freeze-thawing Circle and multi-probe cryosurgery process are further simulated and the characteristic of the thermal field and thermal gradient around cryoprobe are analyzed. The application of enthalpy mathematical model and finite element scheme provide useful simulating means for the cryosurgery and will be beneficial for the progressing and extending of the cryosurgery technology.