Fisetin inhibits growth,induces G2/M arrest and apoptosis of human epidermoid carcinoma A431 cells: role of mitochondrial membrane potential disruption and consequent caspases activation

Non‐melanoma skin cancers (NMSCs), one of the most common neoplasms, cause serious morbidity and mortality. Therefore, identification of non‐toxic phytochemicals for prevention/treatment of NMSCs is highly desirable. Fisetin (3,3′,4′,7‐tetrahydroxyflavone), a dietary flavonoid, present in fruits and vegetables possesses anti‐oxidant and antiproliferative properties. The aim of this study was to investigate the chemotherapeutic potential of fisetin in cultured human epidermoid carcinoma A431 cells. Treatment of A431 cells with fisetin (5–80 μm ) resulted in a significant decrease in cell viability in a dose‐ and time‐dependent manner. Employing clonogenic assay, we found that fisetin treatment significantly reduced colony formation in A431 cells. Fisetin treatment of A431 cells resulted in G₂/M arrest and induction of apoptosis. Furthermore, treatment of A431 cells with fisetin resulted in (i) decreased expression of anti‐apoptotic proteins (Bcl2; Bcl‐xL and Mcl‐1); (ii) increased expression of pro‐apoptotic proteins (Bax, Bak and Bad); (iii) disruption of mitochondrial potential; (iv) release of cytochrome c and Smac/DIABLO from mitochondria; (v) activation of caspases; and (vi) cleavage of Poly(ADP‐ribose) polymerase (PARP) protein. Pretreatment of A431 cells with the pan‐caspase inhibitor (Z‐VAD‐FMK) blocked fisetin‐induced cleavage of caspases and PARP. Taken together, these data provide evidence that fisetin possesses chemotherapeutic potential against human epidermoid carcinoma A431 cells. Overall, these results suggest that fisetin could be developed as a novel therapeutic agent for the management of NMSCs.     

Neuroimaging in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by progressive degeneration of upper motor neurons (UMN) and lower motor neurons (LMN). While LMN dysfunction can be confirmed by electromyography (EMG) and muscle biopsy, UMN involvement is more difficult to detect, particularly in the early phase. Objective and sensitive measures of UMN dysfunction are needed for early diagnosis and monitoring of disease progression and therapeutic efficacy. Advanced magnetic resonance imaging (MRI) techniques, such as diffusion, perfusion, magnetization transfer imaging, functional MRI, and MR spectroscopy, provide insight into the pathophysiological processes of ALS and may have a role in the identification and monitoring of UMN pathology. This article provides an overview of these neuroimaging techniques and their potential roles in ALS.     

The Novel Triad of Dorsal Agenesis of the Pancreas with Concurrent Pancreatic Ductal Adenocarcinoma and Nonalcoholic Chronic Calcific Pancreatitis: A Case Series and Review of the Literature

Introduction  

Dorsal agenesis of the pancreas (DAP) is a rare congenital anomaly, with only 44 cases having been reported in the English literature since 1966.     

Management of upper-airway obstruction in children

The upper airway extends from the nares and lip to the subglottis. Obstruction can occur at any level, and may be congenital or acquired, acute or chronic. The level and severity of the obstruction determine the clinical picture. Whilst a careful history and examination may reveal the diagnosis, investigations are frequently necessary and include physiological studies, imaging and endoscopy. This review discusses the most commonly seen upper-airway disorders, including their presentation and management. An approach to the history and examination is covered, as well as a discussion of the risks and benefits of the most commonly used investigational strategies.     

Determination of Genetic Diversity of the Morinda tinctoria Population in Historical Mandore Garden

Morinda tinctoria (Rubiaceae) commonly called as ‘Indian Mulberry’ is one of the avenue trees of historically important Mandore garden planted anthropogenically in the past. Objective of this study was to determine the genetic diversity of M. tinctoria population at Mandore garden using Random Amplified Polymorphic DNA and Inter Simple Sequence Repeat Markers. A total of 97 bands were produced from 10 random amplified polymorphic DNA primers (49 bands) and 8 inter simple sequence repeat primers (48 bands). No polymorphic bands were obtained in any accessions using the two methods, which strongly suggested that M. tinctoria of this region appear as identical clones. Monomorphic pattern revealed the clonal plantation of M. tinctoria in this historical garden. This is the first report on use of molecular markers to infer the ancient plantation history. Consequences of genetically monomorphic population under global climate changes are discussed and conservation strategy is proposed.     

CYP2C9 allelic variants: ethnic distribution and functional significance

Cytochrome P-450 (CYP) 2C9 CYP2C9 is a polymorphically expressed enzyme responsible for the metabolism of several clinically important drugs, some with a low therapeutic index. This review summarizes the structure-function relationship of the CYP2C9 promoter and coding regions, known polymorphisms, the functional significance of various CYP2C9 alleles in vitro and in vivo, and their population frequencies. In addition, possible molecular mechanisms underlying ethnic variability in the metabolism of CYP2C9 substrate drugs are discussed.     

Multiform cervical melanocytoma: a case report

Melanocytomas are very rare benign melanocytic tumors of the central nervous system (CNS). We present a case of a cervical melanocytoma diagnosed after trauma as a result of persistent neck pain and abnormal neurological examination. Early recognition of benign melanocytic lesions of the CNS is important, as a complete resection can often lead to cure with no need for further treatment.     

Rattlesnake bites in children: antivenin treatment and surgical indications

BACKGROUND: Orthopaedic surgeons working in the Americas may be consulted in the care of patients bitten by venomous rattlesnakes (genus Crotalus ), particularly with regard to the possibilities of compartment syndrome and soft-tissue destruction. Despite considerable evidence regarding the safety and efficacy of antivenin in the treatment of rattlesnake bites in adults, controversy persists regarding the roles of antivenin and surgery in the treatment of rattlesnake envenomations in children. Our hypothesis is that aggressive use of antivenin is just as effective and safe for children as it is for adults. METHODS: We retrospectively reviewed the charts of twenty-four consecutive patients who had been managed at our hospital because of a bite from a western diamondback rattlesnake. Nineteen of the twenty-four patients had been envenomated. The uniformity of collected data was facilitated by the use of an intensive-care-unit protocol during the ten-year period that was reviewed. A questionnaire was developed for long-term follow-up. RESULTS: Aggressive use of polyvalent equine antivenin safely prevented the need for surgery in sixteen of the nineteen envenomated patients. Of the three patients who had surgical treatment, two were managed with limited soft-tissue debridement and one was managed with a fasciotomy of the leg because of a compartment syndrome that occurred when adequate antivenin was withheld. No serious adverse effects were noted in association with the antivenin, and no functional impairments were noted at the time of discharge. CONCLUSION: Antivenin, rather than surgery, is the proper initial treatment of severe rattlesnake envenomations in children.