Search

The overexpression of the human epidermal growth factor 2 (HER2/neu) oncogene is predictive of adverse breast cancer prognosis. Silencing the HER2/neu overexpression using siRNA may be an effective treatment strategy. Major requirements for siRNA-based therapy are safe, stable, and efficient delivery systems to channel siRNA into target cells. This study assessed the efficacy of cationic lipid-based systems for the delivery of siRNA. Cationic liposomes were formulated with equimolar ratios of the respective cholesteryl cytofectins, 3β-N-(N′, N′-dimethylaminopropyl)-carbamoyl cholesterol (Chol-T) or N, N-dimethylaminopropylaminylsuccinylcholesterylformylhydrazide (MS09), with the neutral helper lipid, dioleoylphosphatidylethanolamine (DOPE), with and without a polyethylene glycol stabilizer. All cationic liposomes efficiently bound, compacted, and protected the therapeutic siRNA against nuclease degradation. Liposomes and siRNA lipoplexes were spherical, HER2/neu siRNA transfection in the HER2/neu overexpressing SKBR-3 cells. The non-PEGylated Chol-T-siRNA lipoplexes induced the highest HER2/neu silencing at the mRNA (10000-fold decrease) and protein levels (>111.6-fold decrease), surpassing that of commercially available Lipofectamine 3000 (4.1-fold reduction in mRNA expression). These cationic liposomes are suitable carriers of HER2/neu siRNA for gene silencing in breast cancer.

The last few decades have seen an overwhelming increase in the amount of research carried out on the use of inorganic nanoparticles. More fascinating is the tremendous progress made in the use of chalcogen and chalcogenide nanoparticles in cancer theranostics. These nanomaterials, which were initially synthesized through chemical methods, have now been efficiently produced using different plant materials. The paradigm shift towards the biogenic route of nanoparticle synthesis stems from its superior advantages of biosafety, eco-friendliness, and simplicity, among others. Despite a large number of reviews available on inorganic nanoparticle synthesis through green chemistry, there is currently a dearth of information on the green synthesis of chalcogens and chalcogenides for cancer research. Nanoformulations involving chalcogens such as sulfur, selenium, and tellurium and their respective chalcogenides have recently emerged as promising tools in cancer therapeutics and diagnosis. Similar to other inorganic nanoparticles, chalcogens and chalcogenides have been synthesized using plant extracts and their purified biomolecules. In this review, we provide an up-to-date discussion of the recent progress that has been made in the plant-mediated synthesis of chalcogens and chalcogenides with a special focus on their application in cancer theranostics.

Background: Strategies aimed at inhibiting the expression of the c-myc oncogene could provide the basis for alternative cancer treatment. In this regard, silencing c-myc expression using small interfering RNA (siRNA) is an attractive option. However, the development of a clinically viable, siRNA-based, c-myc silencing system is largely dependent upon the design of an appropriate siRNA carrier that can be easily prepared. Nanostructures formed by the electrostatic association of siRNA and cationic lipid vesicles represent uncomplicated siRNA delivery systems. Methods: This study has focused on cationic liposomes prepared with equimolar quantities of the cytofectin, N,N-dimethylaminopropylamido-succinylcholesteryl-formylhydrazide (MS09), and cholesterol (Chol) for the development of a simple, but effective anti- c-myc onco-nanotherapeutic agent. Liposomes formulated with dioleoylphosphatidylethanolamine (DOPE) in place of Chol as the co-lipid were included for comparative purposes. Results: Liposomes successfully bound siRNA forming lipoplexes of less than 150 nm in size, which assumed bilamellar aggregrates. The liposome formulations were well tolerated in the human breast adenocarcinoma (MCF-7) and colon carcinoma (HT-29) cells, which overexpress c-myc. Lipoplexes directed against the c-myc transcript mediated a dramatic reduction in c-myc mRNA and protein levels. Moreover, oncogene knockdown and anti-cancer effects were superior to that of Lipofectamine™ 3000. Conclusion: This anti- c-myc MS09:Chol lipoplex exemplifies a simple anticancer agent with enhanced c-myc gene silencing potential in vitro

Background: Strategies aimed at inhibiting the expression of the c-myc oncogene could provide the basis for alternative cancer treatment. In this regard, silencing c-myc expression using small interfering RNA (siRNA) is an attractive option. However, the development of a clinically viable, siRNA-based, c-myc silencing system is largely dependent upon the design of an appropriate siRNA carrier that can be easily prepared. Nanostructures formed by the electrostatic association of siRNA and cationic lipid vesicles represent uncomplicated siRNA delivery systems. Methods: This study has focused on cationic liposomes prepared with equimolar quantities of the cytofectin, N,N-dimethylaminopropylamido-succinylcholesteryl-formylhydrazide (MS09), and cholesterol (Chol) for the development of a simple, but effective anti- c-myc onco-nanotherapeutic agent. Liposomes formulated with dioleoylphosphatidylethanolamine (DOPE) in place of Chol as the co-lipid were included for comparative purposes. Results: Liposomes successfully bound siRNA forming lipoplexes of less than 200 nm in size, which assumed globular, bilamellar structures. The liposome formulations were well tolerated in the human breast adenocarcinoma (MCF-7) and colon carcinoma (HT-29) cells, which overexpress c-myc. Lipoplexes directed against the c-myc transcript mediated a dramatic reduction in c-myc mRNA and protein levels. Moreover, oncogene knockdown and anti-cancer effects were superior to that of Lipofectamine™ 3000. Conclusion: This anti- c-myc MS09:Chol lipoplex exemplifies a simple anticancer agent with enhanced c-myc gene silencing potential in vitro.

The concomitant diagnosis of Parkinson's disease (PD) and Myasthenia Gravis (MG) is rare. The aim of the study was to report our experience of patients with both diagnoses. We performed a retrospective analysis of patients with MG and PD, seen at Neurology Department, Modena, Italy from 2000 to 2020. We encountered 12 patients with both diagnoses. All had late onset MG (LOMG) and low Myasthenia Gravis Foundation of America (MGFA) severity scores at baseline. In respect of PD assessement, clinical signs were followed and summarized with modified Hoehn and Yahr staging (mHY). Patients were ranked as progressive or non-progressive, according to any change in mHY staging. We compared characteristics and outcome of the patients with age matched myasthenic subjects without PD. The male gender significantly prevailed (p < 0.01) as well as the presence of multiple comorbidities (p < 0.001) in patients with MG associated with PD. In respect of clinical course, MG was benign as most of cases remained stable (66.7%). Six cases showed worsening of mHY scores; only one subject became wheelchair bound by the end of follow up. This uneven progression, at least in our hands, might suggest that MG and PD can evolve independently. Clinicians should be alert about the association of PD and MG since early diagnosis and treatment are essential. [ABSTRACT FROM AUTHOR]

Bimetallic nanoparticles (BNPs) have shown better biological potential compared to their monometallic counterparts owing to the synergistic effect produced by these alloys. In this study, selenium-capped silver nanoparticles (Ag@Se NPs) were synthesized using an Ocimum tenuiflorum extract. These BNPs were characterized using UV-visible, Fourier transform infrared spectroscopy, nanoparticle tracking analysis, electron microscopy and energy dispersive x-ray analysis. Response surface methodology was used to understand how extract volume and temperature influenced the zeta potential, hydrodynamic size and NP concentration. The phytoconstituents were identified using gas chromatography-mass spectrometry (GC-MS) and molecular docking studies were performed on B-DNA to determine possible genotoxicity. Antioxidant activities, in vitro cytotoxicity (3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay), and genotoxicity (Allium cepa root cells) of these BNPs, were also evaluated. A surface plasmon resonance band around 420 nm confirmed BNP formation with significant quantities of silver and selenium. The Ag@Se NPs displayed good stability, dispersity, antioxidant activity, and compatibility at low concentrations but showed significant cytotoxicity and genotoxicity at high concentrations. Molecular docking analysis showed weak interactions between the plant constituents and B-DNA, suggesting no genotoxicity. These results provide an insight into the conditions required for optimal production of eco-friendly Ag@Se NPs with interesting biological properties.

Background and purpose: The study aimed to identify predictors of respiratory failure leading to mechanical ventilation (MV) and tracheostomy in Guillain−Barré syndrome (GBS). Methods: Two hundred and thirty adult cases admitted to the Neurology Unit of Modena, Italy, between January 2000 and December 2021 were studied. A cut‐off of MV starting within 8 weeks from onset of weakness was used. Univariable, multivariable logistic and Cox regression analyses were used to determine which pre‐specified clinical and diagnostic characteristics were capable of predicting MV and tracheostomy, due to weaning failure. The model was internally validated within the full cohort. The Erasmus GBS Respiratory Insufficiency Score was retrospectively applied. Results: One hundred and seventy‐six cases (76.5%) were classified as classical sensorimotor GBS and 54 (23.4%) as variants. Thirty‐two patients (13.9%) needed MV: 84.3% required respiratory support within 7 days. Independent predictors of respiratory failure and MV were older age, facial, bulbar, neck flexor weakness, dysautonomia, axonal electrophysiological subtype, cardiovascular comorbidities and higher disability score at entry. There was no association with abnormal spinal fluid parameters nor with positive serology for recent infections. Twenty‐two patients (68.7%) were ventilated for more than 7 days; 4.7% died within 8 weeks. The patients who required MV were treated more often with plasma exchange. Independent predictors of tracheostomy due to weaning trial failure were facial, bulbar, neck flexor weakness, autonomic dysfunction, associated cardiovascular morbidities and axonal electrophysiological subtype on nerve conduction study. Conclusions: Our study indicates distinct predictors of MV and tracheostomy in GBS patients. [ABSTRACT FROM AUTHOR]

Overexpression of the c-myc proto-oncogene features prominently in most human cancers. Early studies established that inhibiting the expression of oncogenic c-myc, produced potent anti-cancer effects. This gave rise to the notion that an appropriate c-myc silencing agent might provide a broadly applicable and more effective form of cancer treatment than is currently available. The endogenous mechanism of RNA interference (RNAi), through which small RNA molecules induce gene silencing by binding to complementary mRNA transcripts, represents an attractive avenue for c-myc inhibition. However, the development of a clinically viable, anti-c-myc RNAi-based platform is largely dependent upon the design of an appropriate carrier of the effector nucleic acids. To date, organic and inorganic nanoparticles were assessed both in vitro and in vivo, as carriers of small interfering RNA (siRNA), DICER-substrate siRNA (DsiRNA), and short hairpin RNA (shRNA) expression plasmids, directed against the c-myc oncogene. We review here the various anti-c-myc RNAi-based nanosystems that have come to the fore, especially between 2005 and 2020.

Local economic development (LED) is a process encompassing mobilisation of resources for competitive advantage by locally-owned or managed courses of action, identified through participation and social dialogue, in a strategically defined territory. LED based on sound business principles can contribute to economic growth, job creation and poverty alleviation. The South African Constitution mandates LED to municipalities. Agriculture remains one of the most labour-intensive goods-production sectors with substantial employment linkages. The study centres on whether agriculture can provide an effective strategy for LED in uMshwathi Local Municipality, District Municipality of uMgungundlovu, KwaZulu-Natal, using the research method of the case study and secondary data. LED theories applied embody the principle of value-adding risk management. Locational development-inducing factors and high potential agricultural land for smallholder and organic farming provide comparative and competitive advantage. Agriculture’s significant role to accelerate LED in uMshwathi is confirmed. A grand strategy and functional strategies are proposed.

Cryoproteinaemia is characterised by the presence of detectable proteins in both serum and plasma that precipitate at 4°C and dissolve at 37°C. Cryoglobulins are constituted by immunoglobulins and are detectable in both serum and plasma, whereas cryofibrinogen is detectable only in plasma. The importance of studying cryoproteinemia was the main theme of the meeting held in Modena in March 2023, entitled: Cryoglobulinemia. Laboratory and clinic, a fruitful collaboration for the correct management of a rare pathology - 4th edition, organised by the Italian Society of Clinical Biochemistry and Molecular Biology (SIBioC) and the Italian Association for the fight against Cryoglobulinaemia (ALCRI). The aim of this conference is to promote a dialogue between clinicians and laboratory professionals, highlighting the information that the clinician expects from the laboratory and the critical points that the laboratory faces when performing a test that is still predominantly performed manually. During the meeting, data from three laboratories were presented and compared, and a group of clinicians who deal with cryoproteinemia in different medical fields -- rheumatologists, nephrologists, haematologists, and neurologists -- contributed their experience in treating patients with cryoproteinemia. The collaboration between laboratory and clinic and the respective scientific societies (SIBioC and ALCRI) have made possible to draw a common line to guide both entities in their daily activity. The road seems long and complex, but a common system is emerging from this interaction, the fruits from which patient will benefit. [ABSTRACT FROM AUTHOR]