Sarcopenia among treated cancer patients before and after neoadjuvant chemotherapy: a systematic review and meta-analysis of high-quality studies.

BACKGROUND: Neoadjuvant chemotherapy, used to shrink tumors before surgery, is increasingly applied in clinical practice. However, retrospective studies indicate that it may increase sarcopenia rates and consequently result in an elevated occurrence rate of postoperative severe complications such as severe surgical incision infection, severe respiratory failure, and severe postoperative hemorrhage, especially in the elderly population. Currently, no systematic analysis examines the association between neoadjuvant chemotherapy and sarcopenia. This study aims to fill this gap with a comprehensive meta-analysis focused on this critical aspect of the field. METHODS: A systematic literature search was conducted in the PubMed and Web of Science databases from their inception to January 2024. The included studies encompassed patients who received neoadjuvant chemotherapy and underwent computed tomography (CT) scans both before and after treatment to calculate skeletal muscle index (SMI) or categorize them for the presence of sarcopenia. The determination of sarcopenia status was based on well-established and validated threshold criteria. Data extraction was performed independently by two reviewers. A meta-analysis was employed to estimate the pooled odds ratio (OR) and its corresponding 95% confidence interval (95% CI) to assess the risk of neoadjuvant chemotherapy-induced muscle reduction. RESULTS: In the 14 studies with complete categorical variable data, comprising 1853 patients, 773 patients were identified as having sarcopenia before neoadjuvant treatment and 941 patients had sarcopenia after neoadjuvant therapy. The OR and its 95% CI was calculated as 1.51 [1.31, 1.73]. Among these, 719 patients had digestive system cancer, with 357 patients having sarcopenia before neoadjuvant treatment and 447 patients after, resulting in an OR of 1.74 [1.40, 2.17]. In the remaining 1134 patients with non-digestive system cancers, 416 were identified as having sarcopenia before neoadjuvant treatment, and 494 patients had sarcopenia after, with an OR of 1.37 [1.15, 1.63]. Additionally, in seven studies with complete continuous variable data, including 1228 patients, the mean difference in the change of SMI before and after neoadjuvant treatment was - 1.13 [- 1.65, - 0.62]. After excluding low-quality small-sample studies with fewer than 50 patients, the same trend was observed in the analysis. CONCLUSION: The risk of muscle reduction significantly increases in cancer patients after neoadjuvant chemotherapy and digestive system cancers tend to have a higher risk of developing sarcopenia post-treatment compared to non-digestive system cancers.

Prefrontal cortex-specific Dcc deletion induces schizophrenia-related behavioral phenotypes and fail to be rescued by olanzapine treatment.

Multiple genome studies have discovered that variation in deleted in colorectal carcinoma (Dcc) at transcription and translation level were associated with the occurrences of psychiatric disorders. Yet, little is known about the function of Dcc in schizophrenia (SCZ)-related behavioral abnormalities and the efficacy of antipsychotic drugs in vivo. Here, we used an animal model of prefrontal cortex-specific knockdown (KD) of Dcc in adult C57BL/6 mice to study the attention deficits and impaired locomotor activity. Our results supported a critical role of Dcc deletion in SCZ-related behaviors. Notably, olanzapine rescued the SCZ-related behaviors in the MK801-treated mice but not in the cortex-specific Dcc KD mice, indicating that Dcc play a critical in the mechanism of antipsychotic effects of olanzapine. Knockdown of Dcc in prefrontal cortex results in glutamatergic dysfunction, including defects in glutamine synthetase and postsynaptic maturation. As one of the major risk factors of the degree of antipsychotic response, Dcc deletion-induced glutamatergic dysfunction may be involved in the underlying mechanism of treatment resistance of olanzapine. Our findings identified Dcc deletion-mediated SCZ-related behavioral defects, which serve as a valuable animal model for study of SCZ and amenable to targeted investigations in mechanistic hypotheses of the mechanism underlying glutamatergic dysfunction-induced antipsychotic treatment resistance.

Near-infrared fluorophores methylene blue for targeted imaging of the stomach in intraoperative navigation.

Near-infrared (NIR) fluorescence imaging-guided surgery is increasingly concerned in gastrointestinal surgery because it can potentially improve clinical outcomes. This new technique can provide intraoperative image guidance for surgical margin evaluation and help surgeons examine residual lesions and small tumors during surgery. NIR fluorophores methylene blue (MB) is a promising fluorescent probe because of its safety and intraoperative imaging in the clinic. However, whether MB possesses the potential to perform intraoperative navigation of the stomach and gastric tumors needs to be further explored. Therefore, the current study mainly validated MB's usefulness in animal models' intraoperative imaging of stomach and gastric tumors. NIR fluorophores MB can exhibit specific uptake by the gastric epithelial cells and cancer cells. It is primarily found that MB can directly target the stomach in mice. Interestingly, MB was applied for the NIR imaging of gastric cancer cell xenografts, suggesting that MB cannot specifically target subcutaneous and orthotopic gastric tumors in xenograft models. Thus, it can be concluded that MB has no inherent specificity for gastric tumors but specificity for gastric tissues. Apparently, MB-positive and negative NIR imaging are meaningful in targeting gastric tissues and tumors. MB is expected to represent a helpful NIR agent to secure precise resection margins during the gastrectomy and resection of gastric tumors.

Nerve injury-induced upregulation of apolipoprotein E in dorsal root ganglion participates in neuropathic pain in male mice.

Apolipoprotein E (ApoE) is an apolipoprotein involved in lipid metabolism and is primarily responsible for lipid transport and cholesterol homeostasis in the central nervous system (CNS). The aim of this study is to explore the role of ApoE in the pathological development of neuropathic pain. First, we examined the location of ApoE in the dorsal root ganglion (DRG) and spinal cord in male mice using immunohistochemistry, and found that ApoE was predominantly expressed in DRG satellite glial cells (SGCs) and macrophages and spinal cord astrocytes. Using a spinal nerve ligation (SNL)-induced neuropathic pain mouse model, we found that nerve injury caused an increase in ApoE expression in the injured DRGs, but not in the spinal cord after SNL surgery. Furthermore, we observed reduced SNL-induced pain hypersensitivity in ApoE knockout mice compared to wild-type mice. Moreover, an antisense oligonucleotide (ASO) targeting the Apoe gene sequence, which was microinjected into the DRG or administered intrathecally, not only reduced ApoE expression in DRG but also attenuated SNL-induced pain hypersensitivity. Finally, we found that a tyrosine kinase receptor AXL, which was previously demonstrated to contribute to neuropathic pain, may mediate ApoE function under neuropathic pain condition. In conclusion, our data suggest that ApoE in DRG promote pain hypersensitivity via the DRG membrane receptor AXL in neurons under neuropathic pain conditions. This study revealed a novel mechanism between lipid homeostasis and neuropathic pain.

Cyclophilin D-mediated angiotensin II-induced NADPH oxidase 4 activation in endothelial mitochondrial dysfunction that can be rescued by gallic acid.

Vascular endothelial dysfunction plays a central role in the most dreadful human diseases, including stroke, tumor metastasis, and the coronavirus disease 2019 (COVID-19). Strong evidence suggests that angiotensin II (Ang II)-induced mitochondrial dysfunction is essential for endothelial dysfunction pathogenesis. However, the precise molecular mechanisms remain obscure. Here, polymerase-interacting protein 2 (Poldip 2) was found in the endothelial mitochondrial matrix and no effects on Poldip 2 and NADPH oxidase 4 (NOX 4) expression treated by Ang II. Interestingly, we first found that Ang II-induced NOX 4 binds with Poldip 2 was dependent on cyclophilin D (CypD). CypD knockdown (KD) significantly inhibited the binding of NOX 4 to Poldip 2, and mitochondrial ROS generation in human umbilical vein endothelial cells (HUVECs). Similar results were also found in cyclosporin A (CsA) treated HUVECs. Our previous study suggested a crosstalk between extracellular regulated protein kinase (ERK) phosphorylation and CypD expression, and gallic acid (GA) inhibited mitochondrial dysfunction in neurons depending on regulating the ERK-CypD axis. Here, we confirmed that GA inhibited Ang II-induced NOX 4 activation and mitochondrial dysfunction via ERK/CypD/NOX 4/Poldip 2 pathway, which provide novel mechanistic insight into CypD act as a key regulator of the NOX 4/Poldip 2 axis in Ang II-induced endothelial mitochondrial dysfunction and GA might be beneficial in the treatment of wide variety of diseases, such as COVID-19, which is worthy further research.

Biomarkers of gastric cancer: current advancement.

Gastric cancer (GC) is one of the most prevalent malignant types worldwide, especially in East Asia. Due to its frequently advanced stage at diagnosis, the mortality from GC is high and the prognosis is still unsatisfactory. Thus, early detection using effective screening approaches is vital to decrease the morbidity and mortality of GC. Interestingly, biomarkers can be used for diagnosis, prediction of sensitivity to treatment, and prognosis in GC. The potential biomarkers detectable in liquid biopsies such as circulating tumor cells (CTCs), long non-coding RNAs (lncRNAs), cell-free DNA (cfDNA), microRNAs, and exosomes reveal numerous information regarding the early prediction and the outcomes for GC patients. Additionally, using the novel serum biomarkers has opened up new opportunities for diagnosing and monitoring patients with GC. This review mainly summarizes the novel progress and approaches in GC biomarkers, which could be potentially used for early diagnosis and therapy monitoring. Meanwhile, we also discussed the advantages, disadvantages, and future perspectives of GC biomarkers.

Indocyanine green for targeted imaging of the gall bladder and fluorescence navigation.

Researchers nowadays have devoted extra attention to the different biomedical applications of indocyanine green (ICG), a US Food and Drug Administration-approved fluorescent compound in the fields such as drug delivery, medical imaging and disease diagnosis. In addition, hepatic function evaluation could be conducted by using ICG before surgical procedures and angiographic assessment of blood. Therefore, ICG will be expected to be excellent imaging and targeting agent in various preclinical and clinical model systems. However, whether ICG possesses the potential for the gall bladder's intraoperative imaging guidance needs to be further explored in vivo animal experiments. Herein, near-infrared fluorophores ICG can display the specific uptake by the gall bladder cells and tissues. The dynamic process of biodistribution and the clearance of ICG in vivo in mice are clearly shown in real-time live-body imaging. Furthermore, ICG was rapidly excreted into the bile and lately biodistributed to the stomach after treatment in mice. Meanwhile, the signal-to-background ratio of the gall bladder demonstrated a tremendously higher level compared to other organs (stomach, heart, liver, lung, pancreas, spleen, intestine and duodenum). In conclusion, fluorescence navigation using ICG fluorescence imaging will provide good visualization and detection of the target lesions (gall bladder) in clinics such as diagnostic medical imaging and intraoperative navigation.

Generation of ultra-treatment-resistant schizophrenia patient-derived induced pluripotent stem cell line UJSi002-A.

Schizophrenia is a chronic, serious and disabling mental disorder. Most patients can effectively control their condition through drug treatment, but there are still some patients who are difficult to gain benefits from drug treatment. Among them, the failure to respond to clozapine full-scale treatment is ultra-treatment-resistant schizophrenia. We generated induced pluripotent stem cells (iPSCs) from an ultra-treatment-resistant schizophrenia patient by electroporation of peripheral blood mononuclear cells (PBMCs) with episomal plasmids encoding OCT 4, SOX 2, NANOG, LIN 28, KLF 4 and MYC. The iPSCs demonstrated normal karyotype, expressed pluripotency markers and differentiated into the three germ layers in vivo.

MultiK-MHKS: a novel multiple kernel learning algorithm.

In this paper, we develop a new effective multiple kernel learning algorithm. First, map the input data into m different feature spaces by m empirical kernels, where each generatedfeature space is takenas one viewof the input space. Then through the borrowing the motivating argument from Canonical Correlation Analysis (CCA)that can maximally correlate the m views in the transformed coordinates, we introduce a special term called Inter-Function Similarity Loss R IFSL into the existing regularization framework so as to guarantee the agreement of multi-view outputs. In implementation, we select the Modification of Ho-Kashyap algorithm with Squared approximation of the misclassification errors (MHKS) as the incorporated paradigm, and the experimental results on benchmark data sets demonstrate the feasibility and effectiveness of the proposed algorithm named MultiK-MHKS.