James Yip

Cerebral ischemia-reperfusion (I/R) incites neurologic damage through a myriad of complex pathophysiological mechanisms, most notably, inflammation and oxidative stress. In I/R injury, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) produces reactive oxygen species (ROS), which promote inflammatory and apoptotic pathways, augmenting ROS production and promoting cell death. Inhibiting ischemia-induced oxidative stress would be beneficial for reducing neuroinflammation and promoting neuronal cell survival. Studies have demonstrated that chlorpromazine and promethazine (C+P) induce neuroprotection. This study investigated how C+P minimizes oxidative stress triggered by ischemic injury. Adult male Sprague-Dawley rats were subject to middle cerebral artery occlusion (MCAO) and subsequent reperfusion. 8mg/kg of C+P was injected into the rats when reperfusion was initiated. Neurologic damage was evaluated using infarct volumes, neurological deficit scoring, and TUNEL assays. NOX enzymatic activity, ROS production, protein expression of NOX subunits, manganese superoxide dismutase (MnSOD), and phosphorylation of PKC-δ were assessed. Neural SHSY5Y cells underwent oxygen-glucose deprivation (OGD) and subsequent reoxygenation and C+P treatment. We also evaluated ROS levels and NOX protein subunit expression, MnSOD, and p-PKC-δ/PKC-δ. Additionally, we measured PKC-δ membrane translocation and the level of interaction between NOX subunit (p47^phox) and PKC-δ via coimmunoprecipitation. As hypothesized, treatment with C+P therapy decreased levels of neurologic damage. ROS production, NOX subunit expression, NOX activity, and p-PKC-δ/PKC-δ were all significantly decreased in subjects treated with C+P. C+P decreased membrane translocation of PKC-δ and lowered the level of interaction between p47^phox and PKC-δ. This study suggests that C+P induces neuroprotective effects in ischemic stroke through inhibiting oxidative stress. Our findings also indicate that PKC-δ, NOX, and MnSOD are vital regulators of oxidative processes, suggesting that C+P may serve as an antioxidant.

Gallstone disease is a common pathology of the digestive system with nearly a 10–20% incidence rate among adults. The mainstay of treatment is cholecystectomy, which is commonly associated with physical pain and may also seriously affect a patient’s quality of life. Clinical research suggests that cholelithiasis is closely related to the age, gender, body mass index, and other basic physical characteristics of patients. Clinical research further suggests that the occurrence of cholelithiasis is related to obesity, diabetes, non-alcoholic fatty liver, and other diseases. For this reason, we reviewed the following: genetic factors; excessive liver cholesterol secretion (causing cholesterol supersaturation in gallbladder bile); accelerated growth of cholesterol crystals and solid cholesterol crystals; gallbladder motility impairment; and cardiovascular factors. Herein, we summarize and analyze the causes and mechanisms of cholelithiasis, discuss its correlation with the pathogenesis of related diseases, and discuss possible mechanisms.

Obesity is a highly prevalent public health concern, attributed to multifactorial causes and limited in treatment options. Several comorbidities are closely associated with obesity such as the development of type 2 diabetes mellitus (T2DM), cardiovascular and cerebrovascular diseases, and nonalcoholic fatty liver disease (NAFLD). Bariatric surgery, which can be delivered in multiple forms, has been remarked as an effective treatment to decrease the prevalence of obesity and its associated comorbidities. The different types of bariatric surgery create a variety of new pathways for food to metabolize in the body and truncate the stomach’s caliber. As a result, only a small quantity of food is tolerated, and the body mass index noticeably decreases. This review describes the improvements of obesity and its comorbidities following bariatric surgery and their mechanism of improvement. Additionally, endocrine function improvements after bariatric surgery, which contributes to the patients’ health improvement, are described, including the role of glucagon-like peptide-1 (GLP-1), fibroblast growth factors 19 and 21 (FGF-19, FGF-21), and pancreatic peptide YY (PYY). Lastly, some of the complications of bariatric surgery, including osteoporosis, iron deficiency/anemia, and diarrhea, as well as their potential mechanisms, are described.

TRAP pregnancies involving monochorionic triplets are extremely rare, calculated to be 1 in 4.5 million. We report two cases of monochorionic triplet pregnancies with an acardiac triplet. In one case, the mother was a 33-year-old G2P1 who underwent dilation and evacuation at 20 weeks due to poor prognosis. The other case involved a 21-year-old G1P0 mother presenting in advanced preterm labor at 21 weeks who elected expectant management. Seventeen cases of monochorionic triplets with TRAP were identified in the literature. Invasive intervention was performed in 10 cases; 9 cases resulted in the survival of the nonacardiac twins and 1 case resulted in the survival of 1 fetus. Our two cases had common sonographic features which included polyhydramnios of all fetuses. Placental features shared between both cases included being large for gestational age and velamentous insertion of the acardiac twin. The acardiac twins in both of our cases were hydropic and demonstrated developed pelvis and lower extremities. One had an omphalocele. Most case reports in the literature review demonstrate similar findings. Two cases of monochorionic triplets with TRAP and acardiac twin are herein described. Successful treatment by invasive interventions have been described in this condition, highlighting the importance of early diagnosis.

To demonstrate the role of the rate-limiting and ATP-dependent gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PCK) in oxidative and lactic stress and the effect of phenothiazine on PCK after stroke, a total of 168 adult male Sprague Dawley rats (3 months old, 280–300 g) underwent 2-h intraluminal middle cerebral artery occlusion (MCAO) and reperfusion for 6, 24, 48 h, or 7 days. Phenothiazine (chlorpromazine and promethazine (C+P)) (8 mg/kg) and 3-mercaptopicolinic acid (3-MPA, a PCK inhibitor, 100 μM) were administered at reperfusion onset. The effects of phosphoenolpyruvate, 3-MPA, or PCK knockdown were studied in neuronal cultures subjected to oxygen/glucose deprivation. Reactive oxygen species, lactate, phosphoenolpyruvate (PEP; a gluconeogenic product), mRNA, and protein of total PCK, PCK-1, and PCK-2 increased after MCAO and oxygen–glucose deprivation (OGD). Oxaloacetate (a gluconeogenic substrate) decreased, while PEP and glucose were increased, suggesting reactive gluconeogenesis. These changes were attenuated by phenothiazine, 3-MPA, or PCK shRNA. PCK-1 and -2 existed primarily in neurons, while the effects of ischemic stroke on the PCK expression were seen predominately in astrocytes. Thus, phenothiazine reduced infarction and oxidative/lactic stress by inhibiting PCKs, leading to functional recovery.

Objective: To investigate the perfusion parameters of computed tomography (CT) in hypoxicischemic encephalopathy (HIE) after off-pump coronary artery bypass grafting (OPCABG), and its potential in predicting the occurrence and prognosis of hypoxic-ischemic encephalopathy. Methods: We selected 830 patients. The patients were grouped into: HIE and no HIE. HIE patients were further divided into two groups: poor prognosis and better prognosis. Results: (1) Patients with HIE, who had a history of stroke and hypertension, showed more severe stenosis on CTA and more perfusion abnormalities compared to non-HIE patients (p < 0.05). (2) The differences in frontal, temporal, occipital lobe rTTP, and occipital lobe rMTT in patients with or without HIE were statistically significant (p < 0.05). (3) Logistic regression analysis showed that the difference in occipital lobe rTTP was an independent risk factor for the morbidity in HIE. (4) HIE patients, if they had a history of an abnormal CT, showed poor prognosis (p < 0.05). Furthermore, in these patients, CT images showed significant differences in right frontal, occipital, basal ganglia rTTP, as well as left temporal, occipital, basal ganglia rTTP, as well as frontal lobe rMTT. (5) Three principal components (F1, F2, F3) can be used to generalize all indexes. Conclusion: The difference in occipital lobe rTTP on CTA perfusion may be a potential predictor of HIE. Furthermore, abnormal CT and rTTP may be used for predicting the prognosis in HIE patients. Three principal components (F1 as a reflection of CBF, F2 as reflection of TTP, F3 as a reflection of MTT) can be used to generally describe perfusion parameters.