A Review of Bioactive Compound Effects from Primary Legume Protein Sources in Human and Animal Health.

The global demand for sustainable and nutritious food sources has catalyzed interest in legumes, known for their rich repertoire of health-promoting compounds. This review delves into the diverse array of bioactive peptides, protein subunits, isoflavones, antinutritional factors, and saponins found in the primary legume protein sources-soybeans, peas, chickpeas, and mung beans. The current state of research on these compounds is critically evaluated, with an emphasis on the potential health benefits, ranging from antioxidant and anticancer properties to the management of chronic diseases such as diabetes and hypertension. The extensively studied soybean is highlighted and the relatively unexplored potential of other legumes is also included, pointing to a significant, underutilized resource for developing health-enhancing foods. The review advocates for future interdisciplinary research to further unravel the mechanisms of action of these bioactive compounds and to explore their synergistic effects. The ultimate goal is to leverage the full spectrum of benefits offered by legumes, not only to advance human health but also to contribute to the sustainability of food systems. By providing a comprehensive overview of the nutraceutical potential of legumes, this manuscript sets a foundation for future investigations aimed at optimizing the use of legumes in the global pursuit of health and nutritional security.

A Rare EGFR-SEPT14 Fusion in a Patient with Colorectal Adenocarcinoma Responding to Erlotinib.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Growing evidence supports gene fusions as good candidates for molecularly targeted therapy in CRC. Here we describe a case of a 63-year-old man who had a radical right hemicolectomy procedure 24 months ago. Pathological diagnosis indicated colorectal adenocarcinoma with stage pT4N2bMx. During re-examination in December 2016, positron emission tomography/computed tomography scans indicated relapse with multiple lymph nodes metastasis. Then the patient received a nine-cycle combination treatment of XELOX and bevacizumab and showed progressive disease (PD). Subsequently, the patient was treated with bevacizumab plus FOLFIRI for 2 months before discontinuation because of adverse events. Paraffin sections of postoperative colorectal tissue were subjected to next-generation sequencing, and epidermal growth factor receptor (EGFR) amplification and rare EGFR-SEPT14 fusion were identified. The patient then received erlotinib, an EGFR tyrosine kinase inhibitor (TKI), and achieved a partial response. However, the patient subsequently showed PD, and a new variant, EGFRvIII, appeared in metastasis, which may be involved in erlotinib resistance. We suggest that there is value in treating patients harboring EGFR fusions with EGFR TKI therapy, and EGFR-SEPT14 fusion may be used as a therapeutic target for CRC. KEY POINTS: To the authors' knowledge, this is the first report of EGFR-SEPT14 fusion in colorectal cancer. The patient achieved a partial response after treatment with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib. This report expands the list of gene fusions in colorectal cancer and highlights new targets for the therapeutic intervention. EGFRvIII may be involved in erlotinib resistance, which is rare in colorectal cancer.

Partial Response to Ceritinib in a Patient With Abdominal Inflammatory Myofibroblastic Tumor Carrying a TFG-ROS1 Fusion.

Inflammatory myofibroblastic tumor (IMT), a rare sarcoma, is primarily treated via resection of the mass. However, there is no standard treatment for recurrence or unresectable tumors. Almost 50% of IMTs carry ALK gene rearrangement that can be treated using ALK inhibitors, but therapeutic options for ALK-negative tumors are limited. This report describes a woman aged 22 years with unresectable ALK-negative IMT. Next-generation sequencing revealed a TFG-ROS1 fusion, and she had a partial response to the ROS1 inhibitor ceritinib. This report provides the first published demonstration of a patient with IMT with ROS1 fusion successfully treated using ceritinib. Our study suggests that targeting ROS1 fusions using the small molecule inhibitor shows promise as an effective therapy in patients with IMT carrying this genetic alteration, but this requires further investigation in large clinical trials.

Genistein protects against Aß25-35 induced apoptosis of PC12 cells through JNK signaling and modulation of Bcl-2 family messengers.

BACKGROUND: Deposition of aggregated amyloid beta (Aß) protein is hallmark of Alzheimer's disease, leading to dysfunction and apoptosis of neurons. The isoflavone phytoestrogen compound genistein (Gen) exerts a significant protective effect against Aß25-35 induced neurotoxicity and mitochondrial damage in rat pheochromocytoma (PC12) cells. However, the mechanisms underlying Gen's rescue remain elusive. Therefore we endeavored to research further the molecular mechanisms underlying Gen's inhibition of Aß25-35 induced apoptosis of neurons. RESULTS: We found that Gen dramatically suppressed the activation by Aß25-35 of p-c-Jun N-terminal kinase (p-JNK), and also inhibited the JNK-dependent decreased of Bcl-w and increased of Bim. Furthermore, Gen significantly reduced the cytoplasmic concentrations of cytochrome c and Smac protein as well as caspase-3 activity. Additionally, pretreatment with JNK inhibitor SP600125 effectively suppressed Aß25-35 induced PC12 cell cytotoxicity. CONCLUSION: Taken together, the results suggested that Gen protects PC12 cells from Aß25-35 induced neurotoxicity by interfering with p-JNK activation, thus attenuating the JNK-dependent apoptosis through the mitochondrial pathway. These findings constitute novel insights into the pathway for Aß25-35 toxicity, and the neuroprotective action of Gen.

The effect of geniste on Aß25-35-induced PC12 cell apoptosis through the JNK-dependent Fas pathway.

The ß-amyloid protein (Aß) is considered to be the key factor for inducing Alzheimer's disease (AD). In recent years, the neuroprotective effects of genistein have drawn increasing attention. However, the molecular mechanisms of GEN (genistein) against Aß are unclear. In the present study, we investigated the inhibitory effects of GEN on Aß25-35-induced apoptosis in cultured PC12 cells and the related signaling pathway. Our data show that GEN significantly inhibited Aß25-35-induced apoptosis of PC12 cells. GEN suppressed Aß25-35-induced JNK activation and the JNK-dependent upregulation of Fas/FasL at the mRNA and protein levels induced by Aß25-35 were significantly decreased by GEN. Additionally, GEN inhibited mRNA expression and activity of caspase-3 and caspase-8 induced by Aß25-35. Together, these findings showed that Aß-induced apoptosis of PC12 cells proceeds through the Fas/FasL pathway. The JNK signaling plays a critical role in regulating the anti-apoptotic effects of genistein. Thus, our results suggest that genistein can inhibit Aß-induced apoptosis of PC12 cells through blockage of the JNK activation and subsequent suppression of the JNK-dependent Fas/FasL pathway.

Clinical and molecular characteristics of community-acquired methicillin-resistant Staphylococcus aureus infections in Chinese neonates.

This study aims to characterize the clinical features of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in Chinese neonates, as well as the molecular characteristics and expression of key virulence genes of isolates. Clinical information and molecular characteristics of 130 cases were analyzed. Up to 83.8% patients were affected with late-onset infection. Cesarean delivery was the main delivery route, accounting for 74.6% of the total deliveries. Pneumonia (69, 53.1%) was the most common infection. A total of 38 patients (29.2%) suffered from complications. Moreover, 35 cases (26.9%) were invasive infections, among which 88.6% involved multiple organs and 45.7% suffered from complications. Cesarean section and premature birth were the risk factors for invasive CA-MRSA infection. ST59-MRSA-SCCmecIVa-t437 (54, 41.5%) was the most predominant CA-MRSA clone. The hla expression in the ST59 isolates was higher than that in ST910 (p = 0.02) and the hla expression in ST59-SCCmecV-t437 was higher than that in ST59-SCCmecIVa-t437. Approximately, 46.4% (13/28) of the infections caused by ST59-SCCmecV were invasive. This value is higher than that of ST59-SCCmecVa caused infections (14/59, 23.7%) (p = 0.03). This study showed that neonatal CA-MRSA infections in China readily become invasive, involve multiple organs, and are often accompanied by complications. The SCCmec V clone may be more pathogenic than the SCCmecVIa clone.

Susceptibility to and resistance determinants of fusidic acid in Staphylococcus aureus isolated from Chinese children with skin and soft tissue infections.

This study aims to determine the resistance rates and determinants of fusidic acid among Staphylococcus aureus isolates collected from Chinese pediatric patients with skin and soft tissue infections (SSTIs). Between 2008 and 2009, a total of 186 clinical S. aureus isolates were collected from the pediatric patients with SSTIs, abscess (44.6%) was the most common SSTI in children 0-16 years old. Four clinical isolates (4/186, 2.2%) were resistant to fusidic acid. Two of these isolates were methicillin-resistant S. aureus (MRSA) that carry the fusC gene. The other two isolates were methicillin-sensitive S. aureus (MSSA) that carry the fusB gene. In the two fusB-positive clinical isolates, the fusB gene was located in a transposon-like element that has 99% identity with a pUB101 fragment from S. aureus. The four fusidic acid-resistant clinical isolates were ST1-MRSA-SCCmecV-t127, ST93-MRSA-SCCmecIII-t202, ST680-MSSA-t5415, and ST680-MSSA-t377. The fusidic acid resistance rate of S. aureus isolated from Chinese pediatric patients with SSTIs was low, and the genes fusB and fusC were the main resistance determinants. The transposon-like element that contains the fusB gene might participate in the transmission of fusidic acid resistance genes. This is the first report regarding the emergence of fusidic acid-resistant clinical S. aureus isolates in mainland China.

Superantigen gene profiles and presence of exfoliative toxin genes in community-acquired meticillin-resistant Staphylococcus aureus isolated from Chinese children.

This study aimed to evaluate the distribution of superantigen gene profiles and the presence of exfoliative toxin genes in community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) isolated from Chinese children, and simultaneously to assess virulence gene profiles and genetic background. Of the CA-MRSA isolates, 88.9 % (88/99) harboured toxin genes, with sek as the most frequent toxin gene (62.6  %), followed by seq (61.6  %), seb (60.6  %) and sea (35.4  %). The eta gene was detected only in one ST398-IVa-spa t034 strain. The sed and etd genes were not found in any of the isolates tested. A total of 38 virulence genotypes were observed, of which the genotype seb-sek-seq (27.3  %, 24/88) comprised the majority, followed by sea-seb-sek-seq (18.2  %, 16/88). The enterotoxin gene cluster including seg-sei-sem-sen-seo-seu predominated at a rate of 15.1  %. The relationship among toxin genotypes, toxin genes encoding profiles of mobile genetic elements and genetic background was analysed. Among 66 clonal complex (CC) 59 isolates, 87.9 % (58/66) were positive for toxin genes, and 75.8  % (50/66) harboured the toxin gene combination seb-sek-seq. Among seb-sek-seq-positive CC59 strains, 42.0  % (21/50) also carried the sea gene. CC59 corresponded exclusively to accessory gene regulator 1 (agr-1). The data presented here enhance our current knowledge on the virulence determinants of CA-MRSA.

Macrolide-resistant Streptococcus pyogenes from Chinese pediatric patients in association with Tn916 transposons family over a 16-year period.

To investigate changes in the antimicrobial susceptibility of Streptococcus pyogenes isolates over a 16-year period, 456 group A streptococci isolates were collected from Chinese pediatric patients among 1993 to 1994 and 2005 to 2008. Susceptibilities to antibiotics were performed using agar dilution methods. The macrolide resistance genes ermB, ermTR, mefA, and tetracycline-resistant gene tetM and the int and xis genes of Tn916 family were detected by polymerase chain reaction. All 456 strains were analyzed by emm typing. Selected strains representing each emm type were further characterized by pulsed-field gel electrophoresis. The resistance rates of erythromycin and clindamycin both significantly increased during the 2 sample periods (79.7% versus 94% for erythromycin and 75.4% versus 96.9% for clindamycin). Telithromycin resistance rate increased from 20.37% to 87.93%. Among the macrolide resistance strains, the rate of strains with the genes int, xis, tetM, and ermB increased with time (16.05% versus 86.91%, P < 0.05). The emm1 and emm12 isolates had high rates of ermB gene, which increased after 16 years (65.2% versus 86.23% for emm1 and 7.7% versus 91.8% for emm12). This study demonstrates the increase in macrolide resistance in S. pyogenes in Chinese children over a 16-year period. The phenomenon may be related not only with the shift in the emm types but also with the change of macrolide-resistant mechanisms. The change of Tn916 family among the isolates may be related with the increased resistance.