Herbal or natural medicines as modulators of peroxisome proliferator-activated receptors and related nuclear receptors for therapy of metabolic syndrome

The use of herbal or natural medicines for the treatment of various disorders has a long and extensive history. Many of these herbal medicines are finding their way onto the world market as alternatives to prescribed drugs currently available to treat various disorders/ailments. In particular, hyperlipidaemia is a major risk factor for atherosclerotic coronary vascular disease, which can culminate in mortality in diabetes mellitus. There is overwhelming evidence that patients with type 2 diabetes mellitus often have metabolic syndrome and require a multifactorial intervention including aggressive treatment of arterial hypertension and dyslipidaemia to prevent cardiovascular complications. One of the most active areas of metabolic research into potential treatments is in the role of nuclear receptors as therapeutic targets for both glucose and lipid metabolism. The purpose of this review is to highlight the recent advances made by pharmaceutical and research organizations in identifying biologically active compounds from natural plant products capable of modulating nuclear receptors such as peroxisome proliferator-activated receptors and, to a lesser extent, liver X receptor and farnesoid X receptor. The specific features presented by these receptors provide an in-depth insight into the pathogenesis of metabolic disease and thus, a means of establishing potential mechanisms of action with traditional medicine. In hindsight, the review offers valuable information for rational drug design using known active compounds of plant origin. Further research may ultimately lead to a reduction in both the chronic microvascular complications of type 2 diabetes mellitus and the risk of cardiovascular disease and metabolic syndrome with the use of traditional medicine.     

Burn‐McKeown syndrome with biallelic promoter type 2 deletion in TXNL4A in two siblings

Burn‐McKeown syndrome (BMKS) (MIM# 608572) is a rare condition caused by biallelic variants in TXNL4A. BMKS is characterized by craniofacial dysmorphism, choanal atresia, and normal intellect in affected individuals. BMKS has overlapping clinical features with Treacher Collins syndrome. Till date, 15 families have been described with BMKS. Homozygosity or compound heterozygosity of promoter deletions and null variants in TXNL4A are known to cause most cases of BMKS. We describe the first Indian family with two siblings with BMKS and promoter type 2 deletion in homozygous state.     

成纤维细胞的力学生物学(上)

由于重力、血液的流动及运动的原因，人体会不断受到力的作用。众所周知，结缔组织是承受与传导力的器官，其内的细胞可以通过多种机制将力转化为生物化学信号，但是有些机制尚未完全了解。结缔组织的成纤维细胞就是对力产生反应的细胞，在力的作用下，会通过改变自身细胞外基质（extracellular matrix，ECM）的基因及蛋白质表达的方法维持组织的结构和功能（如创伤修复）。当结缔组织承受到较大的压力时，可以使结缔组织保持正常的功能和组织的动态平衡。结缔组织的修复及维持主要由间充质细胞或成纤维细胞来完成。力可以调节细胞的多种功能，如细胞增殖、基因表达及蛋白质分泌。     

Physiological dead space during general anaesthesia for Caesarean section

The physiological dead space and its components were determined during general anaesthesia for Caesarean section in seventeen patients and compared with similar values for seventeen patients undergoing abdominal hysterectomy under general anaesthesia. The physiological dead space was smaller in the pregnant patients, due to a smaller alveolar dead space. The anatomical dead space was similar in both groups. A lowered physiological dead space suggests that there will be a decrease in the pulmonary ventilation perfusion ratio (V/Q) during Caesarean section; this could result from better perfusion of the ventilated alveoli than in the non-pregnant group, due to the increased cardiac output of pregnancy. An improvement in alveolar perfusion should also produce more efficient carbon dioxide elimination in pregnant patients, when compared to non-pregnant subjects.     

Hyperbaric therapy for a postpartum patient with prolonged epidural blockade and tomographic evidence of epidural air

We used the epidural technique "loss of resistance to air" to provide labor analgesia in a healthy parturient. Inadequate analgesia required epidural catheter replacement using the same technique. Delayed recovery of sensory and motor blockade postpartum necessitated computed tomography and magnetic resonance imaging studies. These revealed 4-6 mL of air in the epidural space with no evidence of thecal compression. On the advice of the neurologist, this patient underwent hyperbaric therapy 14 h after the discontinuation of the epidural infusion. The patient made a complete recovery and was discharged without neurologic sequelae. It is possible that epidural air delayed the absorption of local anesthetics as a result of a reduction in the vascular surface area. Although a cause and effect relationship between epidural air and prolonged neurological block cannot be categorically established, the use of "loss of resistance to air" technique complicated the differential diagnosis. IMPLICATIONS: We report a case of prolonged motor and sensory block after labor analgesia using "loss of resistance to air" technique. The presence of epidural air on tomography resulted in the patient undergoing hyperbaric therapy. The use of loss of resistance to air technique complicated the differential diagnosis of prolonged sensory and motor block.     

Deep sternal wire infection resulting in severe pulmonary valve endocarditis

Right-sided infective endocarditis is uncommon, comprising less than 5% of all cases of endocarditis. This is primarily seen in patients with drug abuse, long-term intravenous catheters, and congenital malformations, or a combination of these. Isolated pulmonary valve endocarditis is difficult to recognize due to its rarity, minimal cardiac manifestations, and predominance of pulmonary infections secondary to embolization of the vegetations. We describe an unusual case of chronic sternal wound infection and migration of an infected braided sternal wire causing right ventricular outflow tract and pulmonary valve endocarditis, which necessitated a complicated reoperation including pulmonary valve replacement with a homograft.     

Multiple oncogenes and tumor suppressor genes are structurally and functionally intact during hepatocarcinogenesis in hepatitis B virus transgenic mice.

In the current study we sought to elucidate the molecular mechanisms which might contribute to hepatocarcinogenesis in a hepatitis B virus (HBV) envelope transgenic mouse model in which chronic hepatocellular injury and inflammation lead to regenerative hyperplasia and eventually to the development of chromosomal abnormalities and hepatocellular carcinoma (HCC), thereby reiterating many of the pathophysiological events that occur prior to the development of HCC in chronic HBV infection in humans. We have previously demonstrated that HBV envelope gene expression is decreased in regenerating hepatocytes and preneoplastic nodules early in the disease process and that expression of alpha-fetoprotein and the multidrug transporter gene mdr-III is activated in the tumors that develop in this model, but not prior to tumor development. In the current study, we examined the structure and expression of a large panel of dominant acting oncogenes and tumor suppressor genes in the liver at all stages of the disease process in order to determine the extent to which they contribute to hepatocarcinogenesis in these transgenic mice. To our surprise, no changes were observed in the structure or function of any of these genes, many of which are commonly activated in other rodent models of hepatocarcinogenesis but rarely activated in human HCC. These findings suggest that the HBV transgenic mouse model is different from most other rodent models of hepatocarcinogenesis and that it may relate more closely to the events involved in HBV-induced human hepatocarcinogenesis, where generalized chromosomal abnormalities are common, while structural and functional changes in most of the commonly studied positive-acting oncogenes examined herein are not. Since p53 and RB mutations have recently been reported to be late events in human hepatocarcinogenesis, the structural integrity of the RB locus and the absence of p53 mutations in the HBV transgenic mouse model suggest that they may represent a relatively early stage of hepatocellular tumorigenesis and that further manipulation of this model is warranted in order to more fully reproduce the molecular-genetic events that characterize HBV-induced HCC in humans.