Isorhamnetin exerts anti-tumor activity in DEN + CCl4-induced HCC mice.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer and the main cause of cancer death globally. The use of medicinal herbs as chemotherapeutic agents in cancer treatment is receiving attention as they possess no or minimum side effects. Isorhamnetin (IRN), a flavonoid, has been under attention for its anti-inflammatory and anti-proliferative properties in a number of cancers, including colorectal, skin, and lung cancers. However, the in vivo mechanism of isorhamnetin to suppress liver cancer has yet to be explored. METHODS AND RESULT: HCC was induced by N-diethylnitrosamine (DEN) and carbon tetrachloride (CCL4) in Swiss albino mice. Isorhamnetin (100 mg/kg body weight) was given to examine its anti-tumor properties in HCC mice model. Histological analysis and liver function assays were performed to assess changes in liver anatomy. Probable molecular pathways were explored using immunoblot, qPCR, ELISA, and immunohistochemistry techniques. Isorhamnetin inhibited various pro-inflammatory cytokines to suppress cancer-inducing inflammation. Additionally, it regulated Akt and MAPKs to suppress Nrf2 signaling. Isorhamnetin activated PPAR-γ and autophagy while suppressing cell cycle progression in DEN + CCl4-administered mice. Additionally, isorhamnetin regulated various signaling pathways to suppress cell proliferation, metabolism, and epithelial-mesenchymal transition in HCC. CONCLUSION: Regulating diverse cellular signaling pathways makes isorhamnetin a better anti-cancer chemotherapeutic candidate in HCC. Importantly, the anti-TNF-α properties of isorhamnetin could prove it a valuable therapeutic agent in sorafenib-resistant HCC patients. Additionally, anti-TGF-ß properties of isorhamnetin could be utilized to reduce the EMT-inducing side effects of doxorubicin.

pH-responsive and targeted delivery of chrysin via folic acid-functionalized mesoporous silica nanocarrier for breast cancer therapy.

Cancer is a disease of global importance. In order to mitigate conventional chemotherapy-related side effects, phytochemicals with inherent anticancer efficacy have been opted. However, the use of nanotechnology is essential to enhance the bioavailability and therapeutic efficacy of these phytochemicals. Herein, we have formulated folic acid conjugated polyacrylic acid capped mesoporous silica nanoparticles (∼47.6 nm in diameter) for pH-dependent targeted delivery of chrysin to breast cancer (MCF-7) cells. Chrysin loaded mesoporous silica nanoparticles (Chr- mSiO2@PAA/FA) have been noted to induce apoptosis in MCF-7 cells through oxidative insult and mitochondrial dysfunction with subsequent G1 arrest. Further, in tumor bearing mice, intravenous incorporation of Chr-mSiO2@PAA/FA has been noticed to enhance the anti-neoplastic effects of chrysin via tumor site-specific accumulation. Enhanced cytotoxicity of chrysin contributed towards in vivo tumor regression, restoration of normalized tissue architecture and maintenance of healthy body weight. Besides, no serious systemic toxicity was manifested in response to Chr-mSiO2@PAA/FA administration in vivo. Thus, the study evokes about the anticancer potentiality of chrysin and its increased therapeutic activity via incorporation into folic acid conjugated mesoporous silica nanoparticles, which may hold greater impact in field of future biomedical research.

Amelioration of oxidative stress mediated inflammation and apoptosis in pancreatic islets by Lupeol in STZ-induced hyperglycaemic mice.

BACKGROUND: Type 1 Diabetes mellitus initiates by loss of pancreatic activity which affects other major organs leading to multi-organ failure. Lupeol, a novel phytochemical, is emerging as a potent bioactive molecule. However, the effect of lupeol on hyperglycaemia is not clearly understood. This study delivers an elaborate vision towards the detailed molecular pathway of lupeol against STZ induced diabetic difficulties of the pancreas. METHOD: The current experiments were designed to focus on the ameliorative effect of the triterpene in combating oxidative damage on the pancreas in a preclinical streptozotocin induced mouse model. After diabetic induction, the animals were subjected to administration with 75 mg kg-1 body weight of lupeol, thrice a week for 7 weeks. Histological measurements were done to investigate the anatomy of the pancreas as well as molecular mechanisms were explored. RESULTS: The compound was found to regulate several hyperglycaemic and oxidative stress related markers. Lupeol treatment also reversed the expression levels of inflammatory cytokines (TNF-α and IL-1ß) as well as attenuated the NF-κB mediated inflammatory and extrinsic apoptotic pathway. DISCUSSION: These findings in preclinical streptozotocin induced in vivo mouse model strongly suggest the discovery of novel properties of lupeol against oxidative stress in pancreatic ß cells by regulating the NF-κB and extrinsic apoptotic pathway.

An overview on the role of bioactive α-glucosidase inhibitors in ameliorating diabetic complications.

Recently the use of bioactive α-glucosidase inhibitors for the treatment of diabetes have been proven to be the most efficient remedy for controlling postprandial hyperglycemia and its detrimental physiological complications, especially in type 2 diabetes. The carbohydrate hydrolysing enzyme, α-glucosidase, is generally competitively inhibited by the α-glucosidase inhibitors and results in the delayed glucose absorption in small intestine, ultimately controlling the postprandial hyperglycemia. Here we have reviewed the most recent updates in the bioactive α-glucosidase inhibitors category. This review provides an overview of the α-glucosidase inhibitory potentials and efficiency of controlling postprandial hyperglycemia of various bioactive compounds such as flavonoids, phenolic compound, polysaccharide, betulinic acid, tannins, anthocyanins, steroids, polyol, polyphenols, galangin, procyanidins, hydroxyl-α-sanshool, hydroxyl-ß-sanshool, erythritol, ganomycin, caffeoylquinic acid, resin glycosides, saponins, avicularin, oleanolic acids, urasolic acid, ethanolic extracts etc., from various dietary and non-dietary naturally occurring sources.

Does posterior half-wedge augmented glenoid restore version and alignment in total shoulder arthroplasty for the B2 glenoid?

INTRODUCTION: Walch type B2 has biconcave glenoid with posterior erosion, bone loss and humeral head subluxation. This leads to decreased glenohumeral contact area and increased contact pressure. During total shoulder arthroplasty(TSA), uncorrected retroversion causes eccentric loading and failure of glenoid component. It also leads to humeral head decentring with posterior rim loading, early glenoid wear and component loosening. This study aims to review anatomical restoration of glenoid version and humeral head centring in TSA with B2 glenoid using CT scans. METHODS: This is a retrospective review of TSA for glenohumeral osteoarthritis with B2 Glenoid morphology. All polyethylene posterior wedge augmented glenoid component was used. All patients underwent pre and post surgery CT Scans. Glenoid version was calculated using neoglenoid line and medial scapular border as reference point. Post-operative humeral head centering was calculated using offset of centre of rotation of humeral head with plane of scapula on axial CT-Scan. RESULTS: Study had 10 patients with 11 TSA between June 2017 and July 2018. Mean age was 59(45-80)years. Mean preoperative retroversion was 16(13-23)degrees. This was corrected to a mean of 0° retroversion postoperatively. 63% had good radiological correction (0-5° retroversion). Humeral head was well centered post-operatively with mean humeral scapula alignment offset of 2.1(0.8-4.5) mm posteriorly. All cases had well-centered humeral head postoperatively with offset less than 5 mm. CONCLUSIONS: Total shoulder replacement in B2 glenoid is technically demanding. Our radiological results show favourable outcome in terms of correction of gelenoid retroversion and eliminating posterior instability using wedge glenoid component. LEVEL OF EVIDENCE: IV.

Ferulic Acid Protects Hyperglycemia-Induced Kidney Damage by Regulating Oxidative Insult, Inflammation and Autophagy.

Oxidative insult, inflammation, apoptosis and autophagy play a pivotal role in the etiology of diabetic nephropathy, a global health concern. Ferulic acid, a phytochemical, is reported to protect against varied diseased conditions. However, the ameliorative role and mechanisms of ferulic acid in averting STZ-mediated nephrotoxicity largely remains unknown. For in vivo study, a single intraperitoneal injection of streptozotocin (50 mg kg-1 body wt.) was administered in experimental rats to induce diabetes. The diabetic rats exhibited a rise in blood glucose level as well as kidney to body weight ratio, a decrease in serum insulin level, severe kidney tissue damage and dysfunction. Elevation of intracellular ROS level, altered mitochondrial membrane potential and cellular redox balance impairment shown the participation of oxidative stress in hyperglycemia-triggered renal injury. Treatment with ferulic acid (50 mg kg-1 body wt., orally for 8 weeks), post-diabetic induction, could markedly ameliorate kidney injury, renal cell apoptosis, inflammation and defective autophagy in the kidneys. The underlying mechanism for such protection involved the modulation of AGEs, MAPKs (p38, JNK, and ERK 1/2), NF-κB mediated inflammatory pathways, mitochondria-dependent and -independent apoptosis as well as autophagy induction. In cultured NRK-52E cells, ferulic acid (at an optimum dose of 75 µM) could counter excessive ROS generation, induce autophagy and inhibit apoptotic death of cells under high glucose environment. Blockade of autophagy could significantly eradicate the protective effect of ferulic acid in high glucose-mediated cell death. Together, the study confirmed that ferulic acid, exhibiting hypoglycemic, antioxidant, anti-inflammatory, anti-apoptotic activities and role in autophagy, could circumvent oxidative stress-mediated renal cell damage.

Taurine ameliorates oxidative stress induced inflammation and ER stress mediated testicular damage in STZ-induced diabetic Wistar rats.

One of the major consequences of diabetes is reproductive dysfunction but the fundamental mechanisms are still poorly known. The objective of the present study was to explore the beneficial role of taurine against streptozotocin induced testicular dysfunctions in diabetic male Wister rats and understanding the underlying intricate molecular mechanisms. Exposure to streptozotocin (50 mg kg-1 body weight, i.p., once) elevated blood glucose level, induced testicular histological alterations and reduced testis-to-body weight ratio, serum testosterone, testicular markers and activity of antioxidant enzymes. Generation of ER stress (increased expression of calpain-1, caspase-12 and upregulation of CHOP, GRP78 via eIF2α signaling), translocation of NF κB in the nucleus (leading to the upregulation in the levels of inflammatory cytokines), activation of mitochondria dependent apoptotic pathway and DNA fragmentation were revealed from this study. However, administration of taurine at a dose of 100 mg kg-1 body weight for 6 weeks post diabetic induction, successfully ameliorated all these adverse effects. Thus, taurine, as a potential therapeutic agent, may hold promise in preventing oxidative and ER stress mediated diabetic testicular complications in rats.

Septic arthritis of the sterno-clavicular joint as a cause of dysphagia: a report of two cases and review of literature.

Septic arthritis of sterno-clavicular joint is a rare entity which is often associated with predisposing conditions like intravenous drug abuse and diabetes. Its prevalence in healthy subjects with absence of medical co-morbidities has been sporadically reported. Due to the rarity of the condition, diagnosis is often delayed predisposing the patients to serious complications. Clinical suspicion supported by haematological and radiological investigations is needed for early diagnosis. Dysphagia as a complication of sterno-clavicular joint infection has not been reported. In this study, we report a case of sterno-clavicular joint infection causing dysphagia and review the literature with regards to aetiology, predisposing factors and treatment options. The aim of this study is to highlight the importance of early diagnosis in suspected cases of septic arthritis of sterno-clavicular joint and institution of intravenous antibiotics.

Anatomical reconstruction of reverse hill-sachs lesions using the underpinning technique.

Posterior glenohumeral joint dislocation is an uncommon injury and is associated with bony and ligamentous disruption. It requires prompt diagnosis and early treatment to prevent acute or recurrent instability and subsequent dysfunction. Reverse Hill-Sachs lesions associated with this injury are challenging to treat, and optimal treatment is controversial. Treatment methods can be divided into those that achieve stability through muscle transfers, osteotomies, or posterior bone-block procedures (glenoid augmentation) and those that restore the sphericity of the humeral head. Joint replacement is often suggested for large head lesions (>50%) considered beyond reconstruction. Restoration of stability, preservation of the proximal humeral anatomy, and salvage of the humeral head sphericity should be the treatment goals in the younger population.This article describes the surgical technique of elevation of the impressed osteochondral fragment followed by filling the lesion with Allomatrix bone graft putty (Wright Medical Technology, Arlington, Tennessee) in 2 patients. The size of the head lesion was ≤35%. Underpinning raft screws were used to provide subchondral support and prevent the collapse of the elevated fragment. Postoperatively, the sphericity of the humeral head and glenohumeral stability were restored. No evidence of collapse, osteonecrosis, or osteoarthritis progression was seen at latest follow-up. Functional results were excellent, with a minimum follow-up of 2 years.This technique is an alternative method of restoring humeral head sphericity in patients with acute posterior glenohumeral joint dislocations with medium (20%-40%) reverse Hill-Sachs lesions.