Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles

Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Activation of the ubiquitin-proteasome system contributes to oculopharyngeal muscular dystrophy through muscle atrophy

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset disorder characterized by progressive weakness and degeneration of specific muscles. OPMD is due to extension of a polyalanine tract in poly(A) binding protein nuclear 1 (PABPN1). Aggregation of the mutant protein in muscle nuclei is a hallmark of the disease. Previous transcriptomic analyses revealed the consistent deregulation of the ubiquitin-proteasome system (UPS) in OPMD animal models and patients, suggesting a role of this deregulation in OPMD pathogenesis. Subsequent studies proposed that UPS contribution to OPMD involved PABPN1 aggregation. Here, we use a Drosophila model of OPMD to address the functional importance of UPS deregulation in OPMD. Through genome-wide and targeted genetic screens we identify a large number of UPS components that are involved in OPMD. Half dosage of UPS genes reduces OPMD muscle defects suggesting a pathological increase of UPS activity in the disease. Quantification of proteasome activity confirms stronger activity in OPMD muscles, associated with degradation of myofibrillar proteins. Importantly, improvement of muscle structure and function in the presence of UPS mutants does not correlate with the levels of PABPN1 aggregation, but is linked to decreased degradation of muscle proteins. Oral treatment with the proteasome inhibitor MG132 is beneficial to the OPMD Drosophila model, improving muscle function although PABPN1 aggregation is enhanced. This functional study reveals the importance of increased UPS activity that underlies muscle atrophy in OPMD. It also provides a proof-of-concept that inhibitors of proteasome activity might be an attractive pharmacological approach for OPMD.

Ceftriaxone for the Treatment of Chronic Bacterial Prostatitis: A Case Series and Literature Review

Chronic bacterial prostatitis is increasingly difficult to treat due to rising antimicrobial resistance limiting oral treatment options. In this case series, 11 men with CBP (including patients with urological comorbidities) due to multi-resistant E. coli were treated with once-daily ceftriaxone intravenously for 6 weeks. Nine patients were clinically cured at 3 months follow up. No early withdrawal of medication due to side effects occurred. A literature review was conducted to describe the prostate pharmacokinetics of ceftriaxone and its use in prostatic infection. In conclusion, ceftriaxone can be considered an appropriate treatment of chronic bacterial prostatitis.

The Effects of Silkworm-Derived Polysaccharide (Silkrose) on Ectoparasitic Infestations in Yellowtail (Seriola quinqueradiata) and White Trevally (Pseudocaranx dentex)

The effect of silkworm-derived polysaccharide silkrose on fish ectoparasites was investigated. When juvenile yellowtail (Seriola quinqueradiata) fed diets containing silkrose were artificially infected with Benedenia seriolae, a fish ectoparasite, the numbers of parasitized B. seriolae were significantly lower compared to that in fish in the control group without silkrose treatment. Furthermore, when juvenile yellowtails were severely infected with B. seriolae, no mortality was observed in the silkrose-treated group, compared to more than 60% in the control group. In field studies carried out at a fish farm with yellowtail and white trevally (Pseudocaranx dentex), oral treatment with silkrose significantly reduced B. seriolae parasitism in yellowtail and Caligus longipedis and Neobenedenia girellae parasitism in white trevally. Silkrose treatment also reduced blood levels of cortisol, a stress hormone in both species. The changes in gene expression in the epidermis of yellowtail by silkrose treatment were also investigated, showing that the expression of various genes, including factors involved in immunity, stress response, and wound healing, was changed by the treatment. These findings indicate that silkworm-derived silkrose effectively prevents infection by external parasites in yellowtail and white trevally.

Impact of the COVID-19 pandemic on the oncologic activities (diagnosis, treatment, clinical trials enrollment) of a general hospital in a district with high prevalence of SARS-COV-2 in Italy

Purpose Little is known about the real impact of the COVID-19 outbreak on the qualitative and quantitative fall-out on the management of cancer patients. Our objective was to provide evidence of the effects of SARS-COV-2 on the management of cancer patients in the real world. Methods In a general hospital in a district in Italy with high prevalence of COVID-19 during the first wave, we retrospectively analyzed the data of oncologic activity, namely new cancer diagnosis, types of treatment (intravenous or by mouth), clinical research studies, and drug utilization, and compared the findings with those of 2019, before the pandemic. The data have been summarized in boxplot figures for median and interquartile range. Results In 2020, a significant reduction in new cancer diagnosis was demonstrated when compared with 2019, with 17.4% fewer cancer diagnoses, 84.5% fewer patients enrolled in clinical trials, a 10.6% reduction in intravenous antitumor treatment, and a 42.7% increase in oral anticancer treatment. Conclusion Our data indicate a significant reduction in cancer diagnosis, antitumor venous treatment, and patients enrolled in clinical research studies in 2020 compared with 2019, although there was a significant increase in oral treatment. These data suggest that the COVID-19 pandemic had a deep impact on the real-world management of cancer patients in a district of Italy with a high prevalence of COVID-19.

COVID-19 Infection Manifesting with Lumbar Spondylodiscitis Complicating With Psoas Abscess without Pneumonia

Extrapulmonary manifestations of COVID-19 (Coronavirus disease 2019) are increasingly recognized. Secondary spinal infections are dangerous complications reported in a few cases in the literature. However, to our knowledge, there is no reported case of a severe spondylodiscitis (SD) complicated with a large psoas abscess in a COVID-19 patient. We would like to report a 43-year-old male patient living in central Anatolia and dealing with farming who presented to the hospital with a complaint of severe back pain. The patient who was given oral treatment with analgesic, anti-inflammatory, and myorelaxant agents was readmitted with increased complaints. His nasopharyngeal swab was positive for COVID-19 without pneumonia on chest computed tomography (CT). He spent the quarantine and treatment period at home but was admitted to our outpatient clinic with a wheelchair with increased complaints and right leg pain preventing daily activities. The control nasopharyngeal swab was negative for COVID-19 but further increase in C-reactive protein (CRP) (152,8 mg/L) and creatine kinase (CK) level (549 IU/L) were revealed. Lumbar magnetic resonance imaging (MRI) showed SD in the L3-L4 level along with right-sided prevertebral inflammatory soft tissue and a large right psoas muscle abscess. Pyogenic lumbar SD complicated with the right psoas abscess in the setting of COVID-19 was considered and antibacterial treatment was started following hospitalization. On the same day, percutaneous aspiration from the psoas abscess under CT guidance was performed and revealed no growth in the culture. After 3 weeks, follow-up MRI showed worsening of all the bone, soft tissue and disc findings. Myalgia is a common manifestation in viral infections, which was also demonstrated in COVID-19 patients, with possible increase in muscle enzymes. Secondary spinal infections and its soft-tissue complications should be considered in the management of COVID-19 patients with neuromuscular symptoms, and detailed neurological and neurosurgical evaluation should be performed in order to avoid progression and permanent damage.

Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive, Improves Cognitive Functions in Mice after Controlled Cortical Impact Injury

Traumatic brain injury (TBI) is a major health concern, sometimes leading to long-term neurological disability, especially in children, young adults and war veterans. Although research investigators and clinicians have applied different treatment strategies or neurosurgical procedures to solve this health issue, we are still in need of an effective therapy to halt the pathogenesis of brain injury. Earlier, we reported that sodium benzoate (NaB), a metabolite of cinnamon and a Food and Drug Administration-approved drug against urea cycle disorders and glycine encephalopathy, protects neurons in animal models of Parkinson’s disease and Alzheimer’s disease. This study was undertaken to examine the therapeutic efficacy of NaB in a controlled cortical impact (CCI)-induced preclinical mouse model of TBI. Oral treatment with NaB, but not sodium formate (NaFO), was found to decrease the activation of microglia and astrocytes and to inhibit the expression of inducible nitric oxide synthase (iNOS) in the hippocampus and cortex of CCI-insulted mice. Further, administration of NaB also reduced the vascular damage and decreased the size of the lesion cavity in the brain of CCI-induced mice. Importantly, NaB-treated mice showed significant improvements in memory and locomotor functions as well as displaying a substantial reduction in depression-like behaviors. These results delineate a novel neuroprotective property of NaB, highlighting its possible therapeutic importance in TBI.

Effect of 7DH biotherapic of Toxoplasma gondii in mice infected with the protozoan

Introduction: Toxoplasmosis is a zoonosis caused by Toxoplasma gondii worldwide distributed [1]. In both, men and animals, the infection with T. gondii can lead to important pathologies [2]. The study of alternative treatments is important to set new therapeutic protocols, especially for the prevention of congenital toxoplasmosis. Aim: This study evaluated the effect of a biotherapic 7DH T. gondii in mice infected with T. gondii. Material and methods: The study was approved by the Ethics Committee for Animal Experimentation of the Universidade Estadual de Maringá – Protocol n° 036/2009. Fourteen mice were used – swiss male aged 57 days divided into two groups according to the treatment (or its diluent biotherapic): BIOT-200DH and Control (cereal alcohol-7%).The biotherapic was prepared with homogenized mouse brain (20 cysts of T.gondii/100μL-average 242 bradyzoites / cyst), according to the Brazilian Homeopathic Pharmacopoeia [3] in laminar flow. The experiment was performed as a blind randomized controlled trial. The animals were treated for 3 days immediately prior to infection. The oral treatment schedule was of 0.1mL/4x/ day, on the first day, followed by 2x/day. Animals aged 57 – 59 days were treated with biotherapic and were clinically evaluated. The animals were orally infected at the age of 60 days (20 cysts ME49-T. gondii). Within18-21 days of infection the clinical parameters were evaluated. On the 55th day of infection the eye fundus was examined (Ophthalmoscope Welch Allyn ®) and the intraocular pressure was measured (Tonometer TONO-PEN ® XL). After 60 days of post-infection the animals were killed in a chamber saturated with halothane, the brains were homogenized and resuspended in 1 ml of saline solution. The cysts were counted according to a rate of 25 mL of suspension, covered with 24x24 mm glass, examined in its full length. Results and discussion: The table 1 summarizes the clinical data. There was no significant difference among the groups for clinical parameters during treatment, although it was recorded the death of an animal in the biotherapic 7DH group. The dead animal presented distended stomach and liquid feces in the intestine. After the infection it was observed reduction of water consumption (p

Pentosan polysulfate inhibits attachment and infection by SARS-CoV-2 in vitro: insights into structural requirements for binding.

Two years since the outbreak of the novel coronavirus SARS-CoV-2 pandemic, there remain few clinically effective drugs to complement vaccines. One is the anticoagulant, heparin, which in 2004 was found able to inhibit invasion of SARS CoV (CoV-1) and which has been employed during the current pandemic to prevent thromboembolic complications and moderate potentially damaging inflammation. Heparin has also been shown experimentally to inhibit SARS-CoV-2 attachment and infection in susceptible cells. At high therapeutic doses however, heparin increases the risk of bleeding and prolonged use can cause heparin-induced thrombocytopenia, a serious side-effect. One alternative, with structural similarities to heparin is the plant-derived, semi-synthetic polysaccharide, pentosan polysulfate (PPS). PPS is an established drug for the oral treatment of interstitial cystitis, is well-tolerated and exhibits weaker anticoagulant effects than heparin. In an established Vero cell model, PPS and its fractions of varying molecular weights, inhibited invasion by SARS-CoV-2. Intact PPS and its size-defined fractions were characterized by molecular weight distribution and chemical structure using NMR spectroscopy and LC-MS, then employed to explore the structural basis of interactions with SARS-CoV-2 spike protein receptor-binding domain (S1 RBD) and the inhibition of Vero cell invasion. PPS was as effective as unfractionated heparin, but more effective at inhibiting cell infection than low molecular weight heparin (on a weight/volume basis). Isothermal titration calorimetry and viral plaque-forming assays demonstrated size-dependent binding to S1 RBD and inhibition of Vero cell invasion, suggesting the potential application of PPS as a novel inhibitor of SARS-CoV-2 infection.