Efficacy of 2-Hydroxyflavanone in Rodent Models of Pain and Inflammation: Involvement of Opioidergic and GABAergic Anti-Nociceptive Mechanisms

The current work examined the pharmacological potential of a selected flavanone derivative 2-hydroxyflavanone as a promising remedy for the treatment and management of pain. The selected flavanone derivative (2-HF) was evaluated for its analgesic and anti-inflammatory potentials following standard pharmacological protocols including hot plate, acetic acid-induced writhing and tail immersion tests. Naloxone and pentylenetetrazol were used to evaluate the potential implication of GABAergic and opioidergic mechanisms. The anti-inflammatory potential of 2-HF was confirmed using carrageenan-, serotonin- and histamine-induced paw edema models as well as a xylene-induced ear edema model. Furthermore, the anti-neuropathic potential of 2-HF was tested using a cisplatin-induced neuropathic pain model. Our sample, at the tested concentrations of 15, 30 and 45 mg kg⁻¹, showed considerable analgesic, anti-inflammatory effects, as well as efficacy against neuropathic pain. Naloxone and pentylenetetrazol at 1 and 15 mg kg⁻¹ antagonized the anti-nociceptive activities of 2-hydroxyflavanone indicating the involvement of opioidergic and GABAergic mechanisms. In the static allodynia model, combination of gabapentin 75 mg kg⁻¹ with 2-HF at 15, 30, 45 mg kg⁻¹ doses exhibited considerable efficacy. In cold allodynia, 2-hydroxyflavanone, at doses of 15, 30 and 45 mg kg⁻¹ and in combination with gabapentin (75 mg kg⁻¹), demonstrated prominent anti-allodynic effects. The paw withdrawal latency was considerably increased in gabapentin + cisplatin treated groups. Moreover, cisplatin + 2-hydroxyflavanone 15, 30, 45 mg kg⁻¹ showed increases in paw withdrawal latency. Likewise, considerable efficacy was observed for 2-hydroxyflavanone in thermal hyperalgesia and dynamic allodynia models. Our findings suggest that 2-hydroxyflavanone is a potential remedy for pain syndrome, possibly mediated through opioidergic and GABAergic mechanisms.     

Metallo-Drugs in Cancer Therapy: Past,Present and Future

Cancer treatments which include conventional chemotherapy have not proven very successful in curing human malignancies. The failures of these treatment modalities include inherent resistance, systemic toxicity and severe side effects. Out of 50% patients administrated to chemotherapy, only 5% survive. For these reasons, the identification of new drug designs and therapeutic strategies that could target cancer cells while leaving normal cells unaffected still continues to be a challenge. Despite advances that have led to the development of new therapies, treatment options are still limited for many types of cancers. This review provides an overview of platinum, copper and ruthenium metal based anticancer drugs in clinical trials and in vitro/in vivo studies. Presumably, copper and ruthenium complexes have greater potential than Pt(II) complexes, showing reduced toxicity, a new mechanism of action, a different spectrum of activity and the possibility of non-cross-resistance. We focus the discussion towards past, present and future aspects.     

HPLC Enantioseparation of Rigid Chiral Probes with Central,Axial, Helical,and Planar Stereogenicity on an Amylose (3,5-Dimethylphenylcarbamate) Chiral Stationary Phase

The chiral resolving ability of the commercially available amylose (3,5-dimethylphenylcarbamate)-based chiral stationary phase (CSP) toward four chiral probes representative of four kinds of stereogenicity (central, axial, helical, and planar) was investigated. Besides chirality, the evident structural feature of selectands is an extremely limited conformational freedom. The chiral rigid analytes were analyzed by using pure short alcohols as mobile phases at different column temperatures. The enantioselectivity was found to be suitable for all compounds investigated. This evidence confirms that the use of the amylose-based CSP in HPLC is an effective strategy for obtaining the resolution of chiral compounds containing any kind of stereogenic element. In addition, the experimental retention and enantioselectivity behavior, as well as the established enantiomer elution order of the investigated chiral analytes, may be used as key information to track essential details on the enantiorecognition mechanism of the amylose-based chiral stationary phase.     

Essential Oils against Sarcoptes scabiei

Herbal remedia are widely employed in folk medicine, and have been more and more often studied and considered in the treatment of several infections. Sarcoptic mange (scabies, when referring to human patients) is a highly contagious skin disease caused by Sarcoptes scabiei (sarcoptiformes, Sarcoptinae), an astigmatid mite which burrows into the epidermis, actively penetrating the stratum corneum. This parasitosis negatively affects livestock productions and represents a constraint on animal and human health. The treatment relies on permethrine and ivermectine but, since these molecules do not have ovicidal action, more than a single dose should be administered. Toxicity, the possible onset of parasite resistance, the presence of residues in meat and other animal products and environmental contamination are the major constraints. These shortcomings could be reduced by the use of plant extracts that have been in vitro or in vivo checked against these mites, sometimes with promising results. The aim of the present study was to review the literature dealing with the treatment of both scabies and sarcoptic mange by plant-derived agents, notably essential oils.     

K18- and CAG-hACE2 Transgenic Mouse Models and SARS-CoV-2: Implications for Neurodegeneration Research

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that might lead to very serious consequences. Notably, mental status change, brain confusion, and smell and taste disorders along with neurological complaints have been reported in patients infected with SARS-CoV-2. Furthermore, human brain tissue autopsies from COVID-19 patients show the presence of SARS-CoV-2 neuroinvasion, which correlates with the manifestation of meningitis, encephalitis, leukocyte infiltration, and neuronal damage. The olfactory mucosa has been suggested as a way of entry into the brain. SARS-CoV-2 infection is also known to provoke a hyper-inflammatory reaction with an exponential increase in the production of pro-inflammatory cytokines leading to systemic responses, even in the absence of direct infection of brain cells. Angiotensin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, has been extensively demonstrated to be present in the periphery, neurons, and glial cells in different brain regions. To dissect the details of neurological complications and develop therapies helping COVID-19 survivors regain pre-infection quality of life, the development of robust clinical models is highly warranted. Several human angiotensin-converting enzyme 2 (hACE2) transgenic mouse models have been developed and used for antiviral drug screening and vaccine development, as well as for better understanding of the molecular pathogenetic mechanisms of SARS-CoV-2 infection. In this review, we summarize recent results from the studies involving two such mouse models, namely K18- and CAG-hACE2 transgenics, to evaluate the direct and indirect impact of SARS-CoV-2 infection on the central nervous system.     

Casorati Inequalities for Statistical Submanifolds in Kenmotsu Statistical Manifolds of Constant ϕ-Sectional Curvature with Semi-Symmetric Metric Connection

In this paper, we prove some inequalities between intrinsic and extrinsic curvature invariants, namely the normalized δ-Casorati curvatures and the scalar curvature of statistical submanifolds in Kenmotsu statistical manifolds of constant ϕ-sectional curvature that are endowed with semi-symmetric metric connection. Furthermore, we investigate the equality cases of these inequalities. We also describe an illustrative example.     

Comparative study of the thermal behavior of Sr–Cu–O gels obtained by sol–gel and microwave-assisted sol–gel method

Journal of Thermal Analysis and Calorimetry - In the literature data, several papers reported the synthesis by various chemical or physical methods of the SrCu2O2 (SCO) having possible applications...     

Recent Advances in Nanotechnology for the Treatment of Melanoma

Melanoma is one of the most aggressive forms of skin cancer, with few possibilities for therapeutic approaches, due to its multi-drug resistance and, consequently, low survival rate for patients. Conventional therapies for treatment melanoma include radiotherapy, chemotherapy, targeted therapy, and immunotherapy, which have various side effects. For this reason, in recent years, pharmaceutical and biomedical research has focused on new sito-specific alternative therapeutic strategies. In this regard, nanotechnology offers numerous benefits which could improve the life expectancy of melanoma patients with very low adverse effects. This review aims to examine the latest advances in nanotechnology as an innovative strategy for treating melanoma. In particular, the use of different types of nanoparticles, such as vesicles, polymers, metal-based, carbon nanotubes, dendrimers, solid lipid, microneedles, and their combination with immunotherapies and vaccines will be discussed.     

A simple,efficient, regioselective and one-pot preparation of N-hydroxy- and N–O-protected hydroxyindoles via cycloaddition of nitrosoarenes with alkynes. Synthetic scope,applications and novel by-products

The thermal reaction between nitrosoarenes and alkynes under alkylating conditions produces N-alkoxyindoles as the major products in moderate to good yields and excellent regioselectivity. Various electrophiles are used affording different N–O-protected hydroxyindoles in a multi-component fashion. Privileged acetylenic substrates used in reactions with substituted nitrosoarenes are arylalkynes or propiolates. Potentially bioactive compounds and other classes of highly functionalizable indole products were prepared. Reactions between o-carbomethoxy-nitrosoarenes and arylacetylenes provided tricyclic compounds containing an acylaziridine indoline skeleton.     

Polymer chain conformation of copolymers with different monomer size: C NMR spectroscopy and MALS study

Copolymer composition, distribution and molecular size of the comonomer influence the final properties of polymer materials. Such influence can be followed from the effect on the chain conformation in solution determined from the scaling law between radius of gyration and molecular weight.