Inwardly rectifying potassium (Kir) channels open at the 'helix bundle crossing' (HBC), formed by the M2 helices at the cytoplasmic end of the transmembrane pore. Introduced negative charges at the HBC (G178D) in Kir2.2 channels forces opening, allowing pore wetting and free movement of permeant ions between the cytoplasm and the inner cavity.
View Article and Find Full Text PDFPhysiological activity of G protein gated inward rectifier K (GIRK, Kir3) channel, dynamically regulated by three key ligands, phosphoinositol-4,5-bisphosphate (PIP), Gβγ, and Na, underlies cellular electrical response to multiple hormones and neurotransmitters in myocytes and neurons. In a reducing environment, matching that inside cells, purified GIRK2 (Kir3.2) channels demonstrate low basal activity, and expected sensitivity to the above ligands.
View Article and Find Full Text PDFInwardly rectifying potassium (Kir) channels play a critical role in stabilizing the membrane potential, thus controlling numerous physiological phenomena in multiple tissues. Channel conductance is activated by cytoplasmic modulators that open the channel at the 'helix bundle crossing' (HBC), formed by the coming together of the M2 helices from each of the four subunits, at the cytoplasmic end of the transmembrane pore. We introduced a negative charge at the bundle crossing region (G178D) in classical inward rectifier Kir2.
View Article and Find Full Text PDFPapillary thyroid cancer (PTC) is the most prevalent histological type of thyroid cancer (TC) worldwide. Although tumor metastasis occurs in regional lymph nodes, distant metastasis (DM) may also occur. Radioactive iodine (RAI) therapy is an effective treatment for TC; however, resistance to RAI occurs in patients with DM.
View Article and Find Full Text PDFJ Gen Physiol
February 2023
Inwardly rectifier potassium (Kir) channels are a major potassium channel sub-class whose function is regulated by ligand-dependent gating and highly voltage-dependent block by polyamines. With molecular dynamics simulations over previously unattainable timescales, Jogini et al. (J.
View Article and Find Full Text PDFRadiation-induced enteritis is frequently observed following radiotherapy for cancer or occurs due to radiation exposure in a nuclear accident. The loss of the epithelial integrity leads to 'leaky gut', so recovery of damaged epithelium is an important strategy in therapeutic trials. (CA), a traditional herbal medicine, is widely used for wound healing by protecting against endothelial damage.
View Article and Find Full Text PDFRadiation-induced cutaneous ulcers are a challenging medical problem for patients receiving radiation therapy. The inhibition of cell senescence has been suggested as a prospective strategy to prevent radiation ulcers. However, there is no effective treatment for senescent cells in radiation ulcers.
View Article and Find Full Text PDFObjective: To investigate the prevalence and oncologic outcomes of patients with multiple primary malignant tumors (MPMT) with gynecologic cancer.
Methods: This retrospective study included 1929 patients diagnosed with gynecologic cancer at a tertiary medical center between August 2005 and April 2021. The clinical data included cancer location, age at primary malignancy diagnosis, interval between primary and secondary cancer, stage of cancer, family history of cancer, genetic testing, dates of last follow-up, recurrence, and death.
Intestinal injury is observed in cancer patients after radiotherapy and in individuals exposed to radiation after a nuclear accident. Radiation disrupts normal vascular homeostasis in the gastrointestinal system by inducing endothelial damage and senescence. Despite advances in medical technology, the toxicity of radiation to healthy tissue remains an issue.
View Article and Find Full Text PDFBackgroud: Exposure to high-dose radiation, such as after a nuclear accident or radiotherapy, elicits severe intestinal damage and is associated with a high mortality rate. In treating patients exhibiting radiation-induced intestinal dysfunction, countermeasures to radiation are required. In principle, the cellular event underlying radiation-induced gastrointestinal syndrome is intestinal stem cell (ISC) apoptosis in the crypts.
View Article and Find Full Text PDFCoronavirus (CoV) outbreaks have recently emerged as a global public health threat due to their exceptional zoonotic potential - a feature arising from their ability to infect a diverse range of potential hosts combined with their high capacity for mutation and recombination. After Severe Acute Respiratory Syndrome (SARS) CoV-1 in 2003 and Middle East Respiratory Syndrome (MERS) CoV in 2012, with the current SARS-CoV-2 pandemic we are now in the midst of the third deadly international CoV outbreak in less than 20 years. Coronavirus outbreaks present a critical threat to global public health and an urgent necessity for therapeutic options.
View Article and Find Full Text PDFIntestinal organoids have recently emerged as an in vitro model relevant to the gut system owing to their recapitulation of the native intestinal epithelium with crypt-villus architecture. However, it is unclear whether intestinal organoids reflect the physiology of the in vivo stress response. Here, we systemically investigated the radiation response in organoids and animal models using mesenchymal stem cell-conditioned medium (MSC-CM), which contains secreted paracrine factors.
View Article and Find Full Text PDFAlthough radiotherapy plays a crucial in the management of pelvic tumors, its toxicity on surrounding healthy tissues such as the small intestine, colon, and rectum is one of the major limitations associated with its use. In particular, proctitis is a major clinical complication of pelvic radiotherapy. Recent evidence suggests that endothelial injury significantly affects the initiation of radiation-induced inflammation.
View Article and Find Full Text PDFPotassium ion conduction through open potassium channels is essential to control of membrane potentials in all cells. To elucidate the open conformation and hence the mechanism of K+ ion conduction in the classic inward rectifier Kir2.2, we introduced a negative charge (G178D) at the crossing point of the inner helix bundle, the location of ligand-dependent gating.
View Article and Find Full Text PDFDelayed wound healing after radiation exposure can cause serious cutaneous damage, and its treatment is a major clinical challenge. Although mesenchymal stem cells (MSCs) have emerged as a promising therapeutic agent in regenerative medicine, they alone do not produce satisfactory effects in a combined radiation and wound injury (CRWI) model. Here, we investigated the therapeutic effect of combined umbilical cord blood-derived (UCB)-MSCs and platelet-rich plasma (PRP) treatment on wound healing in a CRWI mouse model.
View Article and Find Full Text PDFRadiation-induced intestinal injury occurred in application of radiotherapy for abdominal and pelvic cancers or in nuclear accidents. Radiation-induced enteritis may be considered an ideal model of gastrointestinal inflammation. The endothelium is a crucial component of inflammation, and the endothelial dysfunction following radiation exposure induces the intestinal proinflammatory response and progression of radiation enteritis.
View Article and Find Full Text PDFBackground: The skin is impacted by every form of external radiation therapy. However, effective therapeutic options for severe, acute radiation-induced skin reactions are limited. Although platelet-rich plasma (PRP) is known to improve cutaneous wound healing, its effects in the context of high-dose irradiation are still poorly understood.
View Article and Find Full Text PDFRecurrence and chemoresistance in colorectal cancer remain important issues for patients treated with conventional therapeutics. Metformin and phenformin, previously used in the treatment of diabetes, have been shown to have anticancer effects in various cancers, including breast, lung and prostate cancers. However, their molecular mechanisms are still unclear.
View Article and Find Full Text PDFHyaluronic acid synthase 2 (HAS2) is suggested to play a critical role in malignancy and is abnormally expressed in many carcinomas. However, its role in colorectal cancer (CRC) malignancy and specific signaling mechanisms remain obscure. Here, we report that HAS2 was markedly increased in both CRC tissue and malignant CRC cell lines.
View Article and Find Full Text PDFRadiation-induced enteropathy remains a major complication after accidental or therapeutic exposure to ionizing radiation. Recent evidence suggests that intestinal microvascular damage significantly affects the development of radiation enteropathy. Mesenchymal stem cell (MSC) therapy is a promising tool to regenerate various tissues, including skin and intestine.
View Article and Find Full Text PDFPotassium (K) channels exhibit exquisite selectivity for conduction of K ions over other cations, particularly Na. High-resolution structures reveal an archetypal selectivity filter (SF) conformation in which dehydrated K ions, but not Na ions, are perfectly coordinated. Using single-molecule FRET (smFRET), we show that the SF-forming loop (SF-loop) in KirBac1.
View Article and Find Full Text PDFInt J Gynaecol Obstet
March 2019
Objective: To determine the 30-day morbidity rate after hysterectomy for benign disease and identify predictors of 30-day morbidity.
Methods: A retrospective study was conducted among women undergoing hysterectomy for benign indications between January 1, 2010, and December 31, 2015, at Konkuk University Hospital, South Korea. Multivariable regression analysis identified independent factors for morbidity.