Quinoa (Chenopodium quinoa Willd) Bran Saponins Alleviate Hyperuricemia and Inhibit Renal Injury by Regulating the PI3K/AKT/NFκB Signaling Pathway and Uric Acid Transport.

Triterpenoids derived from natural products can exert antihyperuricemic effects. Here, we investigated the antihyperuricemic activity and mechanism of quinoa bran saponins (QBSs) in hyperuricemic mouse and cell models. The QBS4 fraction, with the highest saponin content, was used. Fourier-transform infrared, high-performance liquid chromatography, and ultrahigh-performance liquid chromatography-mass spectrometry identified 11 individual saponins in QBS4, of which the main components were hederagenin and oleanolic acid. The QBS4 effects on hyperuricemic mice (induced by adenine and potassium oxonate) were then studied. QBS4 reduced the levels of uric acid (UA), serum urea nitrogen, creatinine, and lipids in mice with hyperuricemia (HUA) and decreased renal inflammation and renal damage. Molecular analysis revealed that QBS4 may alleviate HUA by regulating the expression of key genes involved in the transport of UA and by inhibiting the activation of the PI3K/AKT/NFκB inflammatory signaling pathway. In conclusion, QBS4 has promise for using as a natural dietary supplement to treat and prevent HUA.

Static Magnetic Field (0.2-0.4 T) Stimulates the Self-Renewal Ability of Osteosarcoma Stem Cells Through Autophagic Degradation of Ferritin.

Static magnetic field (SMF) can alter cell fate decisions in many ways. However, the effects of SMF on cancer stem cells (CSCs) are little-known. In this particular study, we evaluate the biological effect of moderate-intensity SMF on osteosarcoma stem cells (OSCs) and try to clarify the underlying mechanisms of action. First, we demonstrated that prolonged exposure to SMF induced the proliferation and tumorsphere formation in K7M2 and MG63 OSCs. Moreover, SMF promoted the release of ferrous iron (Fe2+ ) and provoked reactive oxygen species (ROS) in OSCs. Interestingly, SMF evidently triggered the autophagic degradation of ferritin, which is characterized by the activation of microtubule-associated protein 1 light chain 3 (LC3) and nuclear receptor co-activator 4 (NCOA4), and downregulation of ferritin heavy chain 1 (FTH1) in OSCs. Particularly, the colony-forming ability of K7M2 OSCs promoted by SMF was obviously abolished by using a small interfering RNA (siRNA) against NCOA4. Finally, treatment of the tumor-bearing mice with SMF did not affect the tumor volume or tumor mass, nor pulmonary metastasis of K7M2 OSCs, but the SMF-treated K7M2 OSCs caused a preference of pulmonary metastasis in a mouse model, which suggested that SMF might induce the metastatic characteristic of OSCs. Consequently, this paper demonstrates for the first time that the cumulative SMF exposure promoted the self-renewal ability of OSCs via autophagic degradation of ferritin, implying that ferritinophagy may be a potential molecular target for cancer. © 2021 Bioelectromagnetics Society.

Ferroptosis, a novel pharmacological mechanism of anti-cancer drugs.

Ferroptosis, a form of regulated cell death, is initiated by oxidative perturbations of the intracellular microenvironment, which is under the constitutive control of glutathione peroxidase 4 (GPX4). Ferrous iron (Fe2+) accumulation and lipid peroxidation are critical events in the induction of ferroptosis, which is inhibited by iron chelators and lipophilic antioxidants. Ferroptosis terminates in mitochondrial dysfunction and toxic lipid peroxidation. It plays a vital role in inhibiting cancer growth and proliferation. It can be induced in cancer cells, and certain normal cells, by experimental compounds (e.g., erastin, Ras-selective lethal small molecule 3) or clinical drugs. The purpose of this review is to summarize the various drugs (e.g., sulfasalazine, lanperisone, sorafenib, fenugreek (trigonelline), acetaminophen, cisplatin, artesunate, combination of siramesine and lapatinib, ferumoxytol, and salinomycin (ironomycin)) that could induce ferroptosis in cancer cells and provide an overview of current knowledge regarding the mechanisms underlying ferroptosis. In future, we anticipate the development of more ferroptosis-inducing drugs, and the availability of such drugs for the clinical treatment of cancer.

Unforgettable Ups and Downs of Acupuncture Anesthesia in China.

BACKGROUND: Acupuncture anesthesia originated from the pain relief and pain prevention theory in acupuncture and moxibustion. This technique is a new exploration of anesthesiology and an original achievement of China, representing a landmark combination of Traditional Chinese Medicine and Western medicine. OBJECTIVES: The aim of this historical vignette to introduce acupuncture anesthesia with its meaningful history, especially the use in neurosurgery to the public. DESIGN: This historical vignette introduced the development, mechanism research, awake craniotomy, in order to analyze the utility of acupuncture anesthesia, its global impact, the current situation and future of acupuncture anesthesia. CONCLUSION: Acupuncture anesthesia was initiated in 1958, and, reflecting the historical background of China after the 1960s, the use of this technique spread widely throughout the country. Reaching other countries after 1971, acupuncture anesthesia had a significant influence, drawing attention from medical academia worldwide. Thus, acupuncture anesthesia has made a special contribution to the medical science of modern China.

Effect of fasudil hydrochloride, a protein kinase inhibitor, on cerebral vasospasm and delayed cerebral ischemic symptoms after aneurysmal subarachnoid hemorrhage.

The efficacy and safety of fasudil hydrochloride, a novel protein kinase inhibitor, were evaluated for the treatment of cerebral vasospasm and associated cerebral ischemic symptoms in patients with ruptured cerebral aneurysm. This randomized open trial with nimodipine as the control included 72 patients who underwent subarachnoid hemorrhage surgery for ruptured cerebral aneurysm of Hunt and Hess grades I to IV. For 14 days following surgery, patients were administered either 30 mg of fasudil hydrochloride by intravenous injection over a period of 30 minutes three times a day or 1 mg/hr of nimodipine by continuous intravenous infusion. Fasudil hydrochloride and nimodipine both showed inhibitory effects on cerebral vasospasm. The incidence of symptomatic vasospasm was five of 33 patients in the fasudil group and nine of 32 patients in the nimodipine group. Good recovery evaluated by the Glasgow Outcome Scale was achieved by 23 of 33 patients in the fasudil group and 19 of 34 patients in the nimodipine group. Both drugs significantly improved consciousness levels and neurological deficits such as aphasia. However, fasudil hydrochloride improved motor disturbance more than nimodipine. Adverse reactions occurred in 13 of 37 patients receiving fasudil hydrochloride and 15 of 35 patients receiving nimodipine. There were no serious adverse events in the fasudil group. The results of this clinical trial indicate that fasudil hydrochloride is a safe and efficient agent for suppressing cerebral vasospasm after subarachnoid hemorrhage surgery for ruptured cerebral aneurysm.

Diagnosis and surgical treatment of brainstem hemangioblastomas.

OBJECTIVE: The study aims to elucidate the advance of diagnosis and surgical treatment of brainstem hemangioblastomas (BSHs). METHODS: The data of the following patients treated in one institute were retrospectively analyzed: (1) patients with a single tumor on the brainstem which was verified by surgery and pathology; (2) patients without von Hippel-Lindau disease or multiple hemangioblastomas. RESULTS: Thirty-three patients with BSHs were identified, accounting for 15.5% of all intracranial hemangioblastomas surgically treated from August 1989 to May 2002 in Huashan Hospital. There were 17 males and 16 females. The patients were aged from 16 to 65 years with an average age of 45 years. The clinical manifestations were nonspecific. Magnetic resonance imaging and digital subtraction angiography were the major diagnostic modalities. Tumors were located on oblongata (14), ponto-oblongata (9), pons (6), and cervicomedulla (4). Tumors were solid in 29 cases, cyst in 4 cases, and had a small size in 5 (< or =3 cm), large in 19 (3.1-4 cm), and giant in 9 (>4 cm). Extra-brainstem (EBS) type (including the fourth-ventricle hemangioblastomas) was seen in 25 cases, and intrabrainstem (IBS) type in 8 cases. Preoperative embolization was performed in 12 cases since 1996. Mild hypothermia with or without hypotension was done during the operation in 10 cases. Total tumor removal was achieved in 31 patients (94%), and incomplete removal in 2 cases. Two patients with EBS type and giant solid tumors died after operation. Follow-up study (range, 1-12 years; mean, 5 years) was available in 31 patients. Karnofsky performance scale scores were > or =80 in 25 patients (80.6%), 60 to 70 in 4 patients (12.9%), and 40 to 50 in 2 patients (6.5%). CONCLUSION: Two types of BSHs can be identified. Patients with cystic IBS type could obtain excellent outcome after operations. Patients with giant or large solid BSHs remain a challenge to neurosurgeons. A combined strategy of preoperative embolization, mild hypothermia with or without hypotension, microsurgical technique, and intensive perioperative management are mandatory for removal of these kinds of tumors with acceptable morbidity and mortality.

Mutation analysis of DMBT1 in glioblastoma, medulloblastoma and oligodendroglial tumors.

DMBT1 has been implicated as a candidate tumor suppressor gene on chromosome 10q for brain, gastrointestinal and lung cancer. Homozygous deletion and lack of expression are 2 known mechanisms for inactivating DMBT1. We evaluated whether somatic mutation, which represents a major inactivation mechanism for most tumor suppressor genes, occurs in the DMBT1 gene. A total of 102 primary brain tumors, consisting of 25 glioblastoma multiforme, 24 medulloblastoma and 53 oligodendroglial tumors, were analyzed by conformation-sensitive gel electrophoresis in all 54 coding exons of DMBT1. Twelve different base substitutions were detected in 26 (25%) tumors. Eight base substitutions resulted in amino acid changes and 4 were silent. These base changes were also detected in tumor-matched blood samples, however, indicating that the base variations represent genetic polymorphisms. We also assessed homozygous deletions of the DMBT1 gene in the series and found that 16 of 95 (5 glioblastomas, 5 medulloblastomas, 6 oligodendroglial tumors; total 17%) tumors harbor such alteration. High-quality blood DNA samples were available in 5 tumors carrying homozygous deletion and, using long-range PCR, 3 of these blood samples showed germline hemizygous deletions in a region between introns 10 and 26 of DMBT1. Our results showed that mutation does not play a role in inactivation of DMBT1 in brain tumors. Intragenic homozygous deletion of DMBT1 is common in brain tumors and is likely a result of a germline deletion of 1 allele followed by loss of the second allele during tumor development.