The Beneficial Effects of Combining Anti-Aβ Antibody NP106 and Curcumin Analog TML-6 on the Treatment of Alzheimer’s Disease in APP/PS1 Mice

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a multifactorial etiology. A multitarget treatment that modulates multifaceted biological functions might be more effective than a single-target approach. Here, the therapeutic efficacy of combination treatment using anti-Aβ antibody NP106 and curcumin analog TML-6 versus monotherapy was investigated in an APP/PS1 mouse model of AD. Our data demonstrate that both combination treatment and monotherapy attenuated brain Aβ and improved the nesting behavioral deficit to varying degrees. Importantly, the combination treatment group had the lowest Aβ levels, and insoluble forms of Aβ were reduced most effectively. The nesting performance of APP/PS1 mice receiving combination treatment was better than that of other APP/PS1 groups. Further findings indicate that enhanced microglial Aβ phagocytosis and lower levels of proinflammatory cytokines were concurrent with the aforementioned effects of NP106 in combination with TML-6. Intriguingly, combination treatment also normalized the gut microbiota of APP/PS1 mice to levels resembling the wild-type control. Taken together, combination treatment outperformed NP106 or TML-6 monotherapy in ameliorating Aβ pathology and the nesting behavioral deficit in APP/PS1 mice. The superior effect might result from a more potent modulation of microglial function, cerebral inflammation, and the gut microbiota. This innovative treatment paradigm confers a new avenue to develop more efficacious AD treatments.

Pre-Clinical Evidence for the Anti-Obesity Potential of Quercetin and Curcumin Loaded Chitosan/PEG Blended PLGA Nanoparticles

This research aimed to formulate quercetin (Qu) and curcumin (CUR)-loaded PLGA NPs coated with chitosan (CS) & PEG and to explore their therapeutic effect against obesity in rats. Qu and CUR nanostructures were prepared and characterized by Zetasizer and TEM. Then, the formulated nanoparticles and their free couterparts were employed for mitigation of obesity in female rats. The size of NPs was in nanometer range with an average size distribution 307.9 nm for Qu NPs and 322.5 nm for CUR NPs. The Qu NPs and CUR NPs were appeared in the TEM image containing core in which the Qu or CUR was localized and surrounded by the coat of PLGA-CS-PEG. The Qu NPs exhibited negative zeta potential at -8.5 mV, while, CUR NPs exhibited positive zeta potential at +0.916 mV. Treatment with orlistat, free Qu, Qu NPs, free CURor CUR NPs elicited significant decline in body weight, BMI and Lee index. Orlistat and CUR NPs significantly diminished liver, heart and visceral adipose tissue weights. Furthermore, the suggested treatments significantly reduced the gonadal and subcutaneous adipose tissue weights. Orlistat significantly lessened kidney and adrenal weights. All treatments significantly minimized serum Chol., TG, LDL, glucose, INS, HOMA-IR, LH, MDA, TLR4 and NF-κB levels and elevated serum HDL, E2 and TAC levels. Orlistat significantly enhanced serum IL-10 level. Conclusively, Qu and CUR nanoformulations offer anti-obesity potency through their hypolipidemic, hypoglycemic,antioxidative and anti-inflammatory effects. Both Qu and CUR NPs manifested superior effect than their free counterparts, may be because of solubility elevation as well as bioavailability of the nanoencapsulation.

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery

Zein, the major storage protein from corn, has a GRAS (Generally Regarded as Safe) status and may be easily transformed into nanoparticles, offering significant payloads for protein materials without affecting their stability. In this work, the capability of bare zein nanoparticles (mucoadhesive) and nanoparticles coated with poly(ethylene glycol) (mucus-permeating) was evaluated as oral carriers of insulin (I-NP and I-NP-PEG, respectively). Both nanocarriers displayed sizes of around 270 nm, insulin payloads close to 80 µg/mg and did not induce cytotoxic effects in Caco-2 and HT29-MTX cell lines. In Caenorhabditis elegans, where insulin decreases fat storage, I-NP-PEG induced a higher reduction in the fat content than I-NP and slightly lower than the control (Orlistat). In diabetic rats, nanoparticles induced a potent hypoglycemic effect and achieved an oral bioavailability of 4.2% for I-NP and 10.2% for I-NP-PEG. This superior effect observed for I-NP-PEG would be related to their capability to diffuse through the mucus layer and reach the surface of enterocytes (where insulin would be released), whereas the mucoadhesive I-NP would remain trapped in the mucus, far away from the absorptive epithelium. In summary, PEG-coated zein nanoparticles may be an interesting device for the effective delivery of proteins through the oral route.

The effect of various fluoride products on dentine lesions during pH-cycling

This study compared the effect of topically applied fluoride products on dentine lesions in an in vitro experiment. Demineralized bovine dentine specimens were treated once with either SDF solution (35,400 ppm F), NaF varnish (22,600 ppm F), TiF4 solution (9,200 ppm F), SnF2 gel (1,000 ppm F), no treatment (control) or preserved as baseline lesions. After the application and subsequent removal of the fluoride products, the specimens were subjected to pH-cycling. Calcium loss and uptake in the de- and remineralization buffers were assessed daily. Fluoride release into the buffers was analyzed on day 1, 2, 3, 5, 8 and 13. After the pH-cycling period, mineral distribution throughout the lesion depth was analyzed using transversal microradiography (TMR). X-ray energy-dispersive spectroscopy (EDS) examined the deposition of silver, titanium and tin after application of SDF, TiF4, and SnF2, respectively. Overall, calcium loss and uptake analysis in the de- and remineralization buffers revealed that the SDF product was the most effective in inhibiting lesion progression, followed by the TiF4, NaF, and SnF2 products. Fluoride analysis disclosed a steep reduction of the amount of fluoride released into de- and remineralization buffers with time. The fluoride effects on de- and remineralization continued beyond the days that fluoride was released into the buffers. TMR analysis showed significant remineralization in the outer zone of the dentine lesions for all fluoride products, with SDF giving hyper-mineralization in this zone. In the inner zone, lesions developed in all fluoride groups, with the smallest in the SDF group. EDS showed silver and titanium deposition in depth up to 85 μm and 8 μm, respectively, while no tin deposition was observed. The silver in the dentine lesions did not contribute significantly to the density of the TMR profiles in the SDF group. In conclusion, all topical fluoride products protected the dentine lesions against lesion progression, but at different degrees. SDF showed a superior effect in protection against further demineralization and enhancement of remineralization. This was probably attributed to its fluoride concentration that was the highest among the fluoride products.

Effects of Exercise during Pregnancy on Postpartum Depression: A Systematic Review of Meta-Analyses

Postpartum depression (PPD) is a public health issue. Exercise is a nonpharmacologic alternative to deal with PPD. This study conducted a systematic review of previous meta-analyses and an exploratory pooled analysis regarding the effects of exercise on depressive symptoms among women during the postpartum period. We searched for previous meta-analyses of randomised controlled trials on PubMed, Web of Science and Scopus, date of inception to 31 May 2021. The methodological quality was assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR2) instrument. We pooled the standardised mean differences from the selected studies. Of the 52 records screened, five were included. The results revealed a significant moderate effect of exercise on depressive symptoms among women during the postpartum period (SMD = −0.53; 95% CI: −0.80 to −0.27, p < 0.001). The pooled effect of the five meta-analyses established that exercise had a significant, small effect on depressive symptoms (SMD = −0.41; 95% CI: −0.50 to −0.32, p < 0.001). Our study indicates that exercise is effective in reducing PPD symptoms. Compared with traditional control approaches (psychosocial and psychological interventions), exercise seems have a superior effect on PPD symptoms. The implications of the present synthesis of past meta-analytical findings to guide health policies and research are discussed.

Novel topical combo-therapeutic formulation integrating honey, neomycin and bacitracin for diabetic wound management

This study evaluated the healing effects of honey as a topical therapy for diabetic ulcers singly and in combination with bacitracin and neomycin (Cicatrin®), formulated as ointments in experimental rats. Antimicrobial evaluation of the test agents against Vancomycin and Oxacillin resistant Staphylococcus aureus (VORSA) and Pseudomonas aeruginosa was done by the cup plate agar-diffusion technique using the Checkerboard method. Subsequently, the optimized combination was formulated into an ointment and administered as single therapy and in combination to hyperglycemic rats made diabetic by subcutaneous injection of alloxan (130 mg/kg) and inflicted with wounds. Administration was done daily on wounds for 21 days while infected wounds had the pus from them evaluated for presence of VORSA and Pseudomonas aeruginosa. The triple combo-therapeutics formulation had improved anti-bacterial activity, in comparison with the individual formulations, with the ratio (1:9) of Cicatrin®: Honey respectively giving the best activity against VORSA. Also, the triple combo-therapeutics exhibited positive wound contraction and size reduction. Furthermore, clinical signs of infection were absent at the end of the follow-up period in the rats administered the combo-therapeutic agents while other groups of rats administered the bland ointment, and the individual agents were infected with either Pseudomonas aeruginosa or VORSA. In addition, the triple combo-therapeutics formulation exhibited good physicochemical stability throughout the treatment duration and beyond (28 days), with insignificant (p > 0.05) changes in pH and spreadability. The triple combination therapeutics formulation showed superior effect to the singly administered agents (honey and Cicatrin®) in the management of diabetic wounds

An Adaptive Rank Aggregation-Based Ensemble Multi-Filter Feature Selection Method in Software Defect Prediction

Feature selection is known to be an applicable solution to address the problem of high dimensionality in software defect prediction (SDP). However, choosing an appropriate filter feature selection (FFS) method that will generate and guarantee optimal features in SDP is an open research issue, known as the filter rank selection problem. As a solution, the combination of multiple filter methods can alleviate the filter rank selection problem. In this study, a novel adaptive rank aggregation-based ensemble multi-filter feature selection (AREMFFS) method is proposed to resolve high dimensionality and filter rank selection problems in SDP. Specifically, the proposed AREMFFS method is based on assessing and combining the strengths of individual FFS methods by aggregating multiple rank lists in the generation and subsequent selection of top-ranked features to be used in the SDP process. The efficacy of the proposed AREMFFS method is evaluated with decision tree (DT) and naïve Bayes (NB) models on defect datasets from different repositories with diverse defect granularities. Findings from the experimental results indicated the superiority of AREMFFS over other baseline FFS methods that were evaluated, existing rank aggregation based multi-filter FS methods, and variants of AREMFFS as developed in this study. That is, the proposed AREMFFS method not only had a superior effect on prediction performances of SDP models but also outperformed baseline FS methods and existing rank aggregation based multi-filter FS methods. Therefore, this study recommends the combination of multiple FFS methods to utilize the strength of respective FFS methods and take advantage of filter–filter relationships in selecting optimal features for SDP processes.

Probióticos en Síndrome de Intestino Irritable: ¿Están listos para la práctica clínica?

Probiotics are used as non-pharmacological therapy for Irritable Bowel Syndrome (IBS). Probiotics have mechanisms of action that can influence the complex pathophysiology of IBS. Evidence of the efficacy and safety of probiotics in IBS is based on various meta-analysis that showed these agents have a limited but superior effect on the management of IBS. The recommendations on the use of probiotics in IBS in the clinical practice guidelines published to date remain controversial. Some recommend the use of probiotics for global symptoms and abdominal pain, while others state that there is low quality evidence for a recommendation. Currently, probiotics are frequently prescribed by doctors for the treatment of patients with IBS. A greater number of high-quality clinical trials are needed to define which probiotic strains are effective in the different IBS phenotypes.

Immunomodulatory Effect of Helleborus purpurascens Waldst. & Kit

(1) Background: Helleborus purpurascens Waldst. & Kit. (hellebore) is a plant species found mainly in Balkans and the Carpathians, and it is traditionally used for a variety of ailments since the time of Hippocrates. The aim of this study was to investigate the immunomodulatory effect of hellebore extracts correlated with relevant chemical compounds and the extraction method. (2) Methods: A methanolic (H1) and a hydroalcoholic extract (H2) were prepared by standard methods. Qualitative (HPTLC) and quantitative (HPLC) chemical analysis were conducted to reveal the ecdysones and polyphenolic compounds. In vitro studies were performed using rat macrophages, murine fibroblasts and immortalized human T-lymphocytes, and their viability was determined by MTS assay. In vivo studies involved a rat immunodepression model. (3) Results: In vitro assays revealed the stronger effect of H2 on cellular proliferation, compared to H1. In the in vivo assay, H2 revealed an immunostimulatory effect in the context of experimentally induced immunosuppression with dexamethasone, a superior effect to levamisole treatment according to the same regimen, in two doses every 24 h. There was no correlation between pharmacological effect and the reference compounds evaluated. (4) Conclusions: The immunomodulatory effect of methanolic and hydroalcoholic hellebore extracts is not due to ecdysones and polyphenolic compounds, but other polar substances, possible steroid glycosides.