Fractionation of Carlina acaulis L. Root Methanolic Extract as a Promising Path towards New Formulations against Bacillus cereus and Methicillin-Resistant Staphylococcus aureus.

The root of Carlina acaulis L. has been widely used in traditional medicine for its antimicrobial properties. In this study, the fractionation of methanol extract from the root was conducted. Four fractions (A, B, C, and D) were obtained and tested against a range of bacteria and fungi. The results showed promising antibacterial activity, especially against Bacillus cereus, where the minimal inhibitory concentration (MIC) was determined to be equal to 0.08 mg/mL and 0.16 mg/mL for heptane (fraction B) and ethyl acetate (fraction C), respectively. In the case of the methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300 strain, the same fractions yielded higher MIC values (2.5 and 5.0 mg/mL, respectively). This was accompanied by a lack of apparent cytotoxicity to normal human BJ foreskin fibroblasts, enterocytes derived from CaCo2 cells, and zebrafish embryos. Further analyses revealed the presence of bioactive chlorogenic acids in the fractionated extract, especially in the ethyl acetate fraction (C). These findings support the traditional use of the root from C. acaulis and pave the way for the development of new formulations for treating bacterial infections. This was further evaluated in a proof-of-concept experiment where fraction C was used in the ointment formulation, which maintained high antimicrobial activity against MRSA and displayed low toxicity towards cultured fibroblasts.

Exposure to Chlorpyrifos Alters Proliferation, Differentiation and Fatty Acid Uptake in 3T3-L1 Cells.

Organophosphorus pesticides (OPs) are important factors in the etiology of many diseases, including obesity and type 2 diabetes mellitus. The aim of this study was to investigate the effect of a representative of OPs, chlorpyrifos (CPF), on viability, proliferation, differentiation, and fatty acid uptake in 3T3-L1 cells. The effect of CPF exposure on preadipocyte proliferation was examined by the MTT, NR, and BrdU assays. The impact of CPF exposure on the differentiation of preadipocytes into mature adipocytes was evaluated by Oil Red O staining and RT-qPCR. The effect of CPF on free fatty acid uptake in adipocytes was assessed with the fluorescent dye BODIPY. Our experiments demonstrated that exposure to CPF decreased the viability of 3T3-L1 cells; however, it was increased when the cells were exposed to low concentrations of the pesticide. Exposure to CPF inhibited the proliferation and differentiation of 3T3-L1 preadipocytes. CPF exposure resulted in decreased lipid accumulation, accompanied by down-regulation of the two key transcription factors in adipogenesis: C/EBPα and PPARγ. Exposure to CPF increased basal free fatty acid uptake in fully differentiated adipocytes but decreased this uptake when CPF was added during the differentiation process. Increased free fatty acid accumulation in fully differentiated adipocytes may suggest that CPF leads to adipocyte hypertrophy, one of the mechanisms leading to obesity, particularly in adults. It can therefore be concluded that CPF may disturb the activity of preadipocytes and adipocytes, although the role of this pesticide in the development of obesity requires further research.

Esketamine and Psilocybin-The Comparison of Two Mind-Altering Agents in Depression Treatment: Systematic Review.

This publication discusses two compounds belonging to the psychoactive substances group which are studied in the context of depression treatment-psilocybin and esketamine. The former is a naturally occurring psychedelic. The latter was invented in the laboratory exactly 60 years ago. Although the substances were controversial in the past, recent studies indicate the potential of those substances as novel antidepressant agents. The PubMed/MEDLINE database was used to identify articles for systematic review, using the following search terms: (depression) AND (psilocybin) OR (ketamine). From 617 items, only 12 articles were obtained in the final analyses. Three articles were devoted to psilocybin in depression treatment and nine to esketamine. In most studies, esketamine showed a significant reduction in both depressive symptoms and suicidal ideation shortly after intake and after a month of treatment compared to baseline and to standard-of-care antidepressant agents. Psilocybin's antidepressive effects occurred one day after intake and after 6-7 weeks of treatment and were maintained for up to 6 or 8 months of follow-up. One study indicated that psilocybin's effects are comparable with and may be superior to escitalopram treatment. Both esketamine and psilocybin demonstrated rapid and long-term effects in reducing depression symptoms and, after overcoming some limitations, may be considered as novel antidepressant agents in future.

Carlina oxide inhibits the interaction of SARS-CoV-2 S glycoprotein with angiotensin-converting enzyme 2.

Carlina acaulis plant is a potential target for the industrial production of phytochemicals that display applicability in pharmacy and medicine. The dry roots of C. acaulis contain up to 2 % of essential oil, the main component (up to 99 %) of which is carlina oxide [2-(3-phenylprop-1-ynyl)furan]. This compound shows multidirectional biological activity, including antibacterial and antifungal properties. Here, we evaluated the capacity of carlina oxide to inhibit the interaction between SARS-CoV-2 and its human receptor in vitro and in silico. A bioluminescent immunoassay was used to study the interaction between the receptor binding domain (RBD) of viral spike protein and the human angiotensin-converting enzyme 2 (ACE2), which serves as a receptor for viral entry. A dose-effect relationship was demonstrated, and a concentration of carlina oxide causing half-maximal inhibition (IC50) of the RBD:ACE2 interaction was determined to be equal to 234.2 µg/mL. Molecular docking suggested the presence of carlina oxide binding sites within the RBD and at the interface between RBD and ACE2. Finally, this study expands the list of potential applications of C. acaulis as a crop species.

Antiproliferative Properties of Triterpenoids by ECIS Method-A New Promising Approach in Anticancer Studies?

Electric cell-substrate impedance sensing is an advanced in vitro impedance measuring system which uses alternating current to determine behavior of cells in physiological conditions. In this study, we used the abovementioned method for checking the anticancer activities of betulin and betulinic acid, which are some of the most commonly found triterpenes in nature. In our experiment, the threshold concentrations of betulin required to elicit antiproliferative effects, verified by MTT and LDH release methods, were 7.8 µM for breast cancer (T47D), 9.5 µM for lung carcinoma (A549), and 21.3 µM for normal epithelial cells (Vero). The ECIS results revealed the great potential of betulin and betulinic acid's antitumor properties and their maintenance of cytotoxic substances to the breast cancer T47D line. Moreover, both substances showed a negligible toxic effect on healthy epithelial cells (Vero). Our investigation showed that the ECIS method is a proper alternative to the currently used assay for testing in vitro anticancer activity of compounds, and that it should thus be introduced in cellular routine research. It is also a valuable tool for live-monitoring changes in the morphology and physiology of cells, which translates into the accurate development of anticancer therapies.

Chlorpyrifos alters expression of enzymes involved in vitamin D3 synthesis in skin cells.

Skin acts as a mechanical barrier between human body and environment. Epidermal cells are regularly exposed to many physiological and environmental stressors, such as pesticides, like chlorpyrifos (CPS). It is recognised that CPS may affect metabolism of other exo- and endogenous substances by affecting enzyme activity and expression. This study aims to investigate the effect of CPS on expression of CYP27A1, CYP27B1 and CYP24A1, the enzymes involved in synthesis and metabolism of vitamin D3, in human keratinocytes HaCaT and human fibroblasts BJ. Synthesis of vitamin D3 in cells was initiated by irradiating with UVB. Expression of CYP27A1, CYP27B1 and CYP24A1 was evaluated by RT-qPCR and Western blot. Our experiments revealed that expression of all tested cytochrome P450 isoforms in cells exposed to CPS changed significantly. Exposure of HaCaT keratinocytes to CPS decreased CYP27A1 mRNA levels, but increased CYP27B1 and CYP24A1 mRNA levels. This was confirmed at the protein level, except for the CYP27A1 expression. Outcome for the BJ cells was however less conclusive. Though exposure to CPS decreased CYP27A1 and CYP27B1 mRNA levels, at protein level increasing concentration of CPS and UVB intensity induced expression of CYP27A1 and CYP24A1. The expression of CYP27B1 isoform decreased in line with mRNA level. Nevertheless, it can be concluded that CPS may therefore interrupt vitamin D3 metabolism in skin cells, but further studies are required to better understand such mechanisms.

Alterations in Kynurenine and NAD+ Salvage Pathways during the Successful Treatment of Inflammatory Bowel Disease Suggest HCAR3 and NNMT as Potential Drug Targets.

A meta-analysis of publicly available transcriptomic datasets was performed to identify metabolic pathways profoundly implicated in the progression and treatment of inflammatory bowel disease (IBD). The analysis revealed that genes involved in tryptophan (Trp) metabolism are upregulated in Crohn's disease (CD) and ulcerative colitis (UC) and return to baseline after successful treatment with infliximab. Microarray and mRNAseq profiles from multiple experiments confirmed that enzymes responsible for Trp degradation via the kynurenine pathway (IDO1, KYNU, IL4I1, KMO, and TDO2), receptor of Trp metabolites (HCAR3), and enzymes catalyzing NAD+ turnover (NAMPT, NNMT, PARP9, CD38) were synchronously coregulated in IBD, but not in intestinal malignancies. The modeling of Trp metabolite fluxes in IBD indicated that changes in gene expression shifted intestinal Trp metabolism from the synthesis of 5-hydroxytryptamine (5HT, serotonin) towards the kynurenine pathway. Based on pathway modeling, this manifested in a decline in mucosal Trp and elevated kynurenine (Kyn) levels, and fueled the production of downstream metabolites, including quinolinate, a substrate for de novo NAD+ synthesis. Interestingly, IBD-dependent alterations in Trp metabolites were normalized in infliximab responders, but not in non-responders. Transcriptomic reconstruction of the NAD+ pathway revealed an increased salvage biosynthesis and utilization of NAD+ in IBD, which normalized in patients successfully treated with infliximab. Treatment-related changes in NAD+ levels correlated with shifts in nicotinamide N-methyltransferase (NNMT) expression. This enzyme helps to maintain a high level of NAD+-dependent proinflammatory signaling by removing excess inhibitory nicotinamide (Nam) from the system. Our analysis highlights the prevalent deregulation of kynurenine and NAD+ biosynthetic pathways in IBD and gives new impetus for conducting an in-depth examination of uncovered phenomena in clinical studies.

Evaluation of Antioxidative Mechanisms In Vitro and Triterpenes Composition of Extracts from Silver Birch (Betula pendula Roth) and Black Birch (Betula obscura Kotula) Barks by FT-IR and HPLC-PDA.

Silver birch, Betula pendula Roth, is one of the most common trees in Europe. Due to its content of many biologically active substances, it has long been used in medicine and cosmetics, unlike the rare black birch, Betula obscura Kotula. The aim of the study was therefore to compare the antioxidant properties of extracts from the inner and outer bark layers of both birch trees towards the L929 line treated with acetaldehyde. Based on the lactate dehydrogenase test and the MTT test, 10 and 25% concentrations of extracts were selected for the antioxidant evaluation. All extracts at tested concentrations reduced the production of hydrogen peroxide, superoxide anion radical, and 25% extract decreased malonic aldehyde formation in acetaldehyde-treated cells. The chemical composition of bark extracts was accessed by IR and HPLC-PDA methods and surprisingly, revealed a high content of betulin and lupeol in the inner bark extract of B. obscura. Furthermore, IR analysis revealed differences in the chemical composition of the outer bark between black and silver birch extracts, indicating that black birch may be a valuable source of numerous biologically active substances. Further experiments are required to evaluate their potential against neuroinflammation, cancer, viral infections, as well as their usefulness in cosmetology.

Serum Level of Metalloproteinase-2 but not Metalloproteinase-9 Rises in Patients With Failed Back Surgery Syndrome After Spinal Cord Stimulation.

OBJECTIVES: The impact of spinal cord stimulation (SCS) on serum levels of metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) was assessed in a group of patients with failed back surgery syndrome (FBSS). The study was to give new insights into the SCS mechanism of action and the role of MMP-2 and MMP-9 in the development of NP. MATERIAL AND METHODS: Clinical assessments were performed and biochemical markers were determined in two groups of patients: the control group (24 individuals) and the FBSS group (24 patients). Seventeen patients with the FBSS had SCS implanted and were examined before surgical procedure, one month after (17 patients), and three months after operation (12 patients). Clinical status was assessed with the use numeric rating scale, pain rating index of McGill pain questionnaire, Oswestry disability index and Beck depression inventory. MMP-2 and MMP-9 serum levels were determined using gelatin zymography. Immunoenzymatic method was employed to determine plasma concentrations of tissue inhibitors of metalloproteinases (TIMPs). RESULTS: Levels of MMP-2 and TIMP-2 were higher in the FBSS group compared to the control group. The difference was statistically significant (p < 0.001 and p = 0.004, respectively). The concentration of MMP-2 was significantly increased (p = 0.0135) one-month post-SCS and remained elevated but stable up to three months after implantation. TIMP-2, MMP-2/TIMP-2, MMP-9, TIMP-1, and MMP-9/TIMP-1 serum levels did not change significantly. CONCLUSIONS: MMPs may play a role in the development of FBSS. SCS increases the already elevated MMP-2 serum levels which are associated with neuroinflammatory processes in FBSS patients.

The Oxidative Stress in Knee Osteoarthritis Patients. An Attempt of Evaluation of Possible Compensatory Effects Occurring in the Disease Development.

Background and Objective: Osteoarthritis (OA) is a disorder of the musculoskeletal system resulting in worsening of life condition. The research revealed the involvement of oxidative stress into both OA pathogenesis and the effects of therapeutic agents applied in OA cases. The activities of the most important antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and total antioxidant status (TAS), in blood of the knee OA patients were studied, with the aim of clarifying which enzymatic antioxidants are involved into osteoarthritis (OA)-related oxidative stress and whether any compensatory effects occur. The results were additionally analyzed with regard to gender. Methods: Whole blood SOD (U/mL), plasma GPx (U/L) and CAT (U/mL) activities as well as plasma TAS (mmol/L)) in knee OA patients were investigated. Sixty-seven patients (49 females and 18 males) with primary knee OA were enrolled. The control comprised 21 subjects (10 females and 11 males) free of osteoarthritis or inflammation. Results: TAS was decreased in OA subjects (4.39 0.53 vs. 4.70 0.60), with this effect being more significant in OA females (4.31 0.51 vs. 5.02 0.54). GPx was depressed in all OA patients (518 176 vs. 675 149). In both genders, GPx was decreased, significantly in males (482 185 vs. 715 105). SOD was decreased in all OA patients (109 32 vs. 127 42). CAT showed no difference in all OA subjects vs. control, while in OA females it was depleted (20.2 (11.6-31.6) vs. 38.5 (27.9-46.6)) and in OA men it increased (26.9 (23.3-46.5) vs. 14.0 (7.0-18.6)). Conclusions: The obtained results suggest that in men some compensatory mechanisms towards OA-related oxidative stress occurred. Based on the obtained data, the introduction of antioxidant supplements into OA therapy could be suggested with further research concerning the choice of agents.

The Influence of Manganese and Glutamine Intake on Antioxidants and Neurotransmitter Amino Acids Levels in Rats' Brain.

Depending on the concentration, Mn can exert protective or toxic effect. Potential mechanism for manganese neurotoxicity is manganese-induced oxidative stress. Glutamine supplementation could reduce manganese-induced neurotoxicity and is able to influence the neurotransmission processes. The aim of this study was to investigate whether the long term administration of manganese (alone or in combination with glutamine) in dose and time dependent manner could affect the selected parameters of oxidative-antioxidative status (superoxide dismutase and glutathione peroxidase activities, concentrations of vitamin C and malonic dialdehyde) and concentrations of excitatory (Asp, Glu) and inhibitory amino acids (GABA, Gly) in the brain of rats. The experiments were carried out on 2-months-old albino male rats randomly divided into 6 group: Mn300 and Mn500-received solution of MnCl2 to drink (dose 300 and 500 mg/L, respectively), Gln group-solution of glutamine (4 g/L), Mn300-Gln and Mn500-Gln groups-solution of Mn at 300 and 500 mg/L and Gln at 4 g/L dose. The control group (C) received deionized water. Half of the animals were euthanized after three and the other half-after 6 weeks of experiment. The exposure of rats to Mn in drinking water contributes to diminishing of the antioxidant enzymes activity and the increase in level of lipid peroxidation. Glutamine in the diet admittedly increases SOD and GPx activity, but it is unable to restore the intracellular redox balance. The most significant differences in the examined amino acids levels in comparison to both control and Gln group were observed in the group of rats receiving Mn at 500 mg/L dose alone or with Gln. It seems that Gln is amino acid which could improve antioxidant status and affect the concentrations of the neurotransmitters.

Homeostasis of chosen bioelements in organs of rats receiving lithium and/or selenium.

Lithium is an essential trace element, widely used in medicine and its application is often long-term. Despite beneficial effects, its administration can lead to severe side effects including hyperparathyroidism, renal and thyroid disorders. The aim of the current study was to evaluate the influence of lithium and/or selenium treatment on magnesium, calcium and silicon levels in rats' organs as well as the possibility of using selenium as an adjuvant in lithium therapy. The study was performed on rats divided into four groups (six animals each): control-treated with saline; Li-treated with Li2CO3 (2.7 mg Li/kg b.w.); Se-treated with Na2SeO3·H2O (0.5 mg Se/kg b.w.); Se + Li-treated simultaneously with Li2CO3 and Na2SeO3·H2O (2.7 mg Li/kg b.w. and of 0.5 mg Se/kg b.w., respectively). The administration was performed in form of water solutions by stomach tube once a day for 3 weeks. In the organs (liver, kidney, brain, spleen, heart, lung and femoral muscle) the concentrations of magnesium, calcium and silicon were determined. Magnesium was increased in liver of Se and Se + Li given rats. Lithium decreased tissue Ca and co-administration of selenium reversed this effect. Silicon was not affected by any treatment. The beneficial effect of selenium on disturbances of calcium homeostasis let suggest that further research on selenium application as an adjuvant in lithium therapy is worth being performed.

Mephedrone and nicotine: oxidative stress and behavioral interactions in animal models.

The purpose of our experiment was to examine the influence of co-administration of nicotine and mephedrone on anxiety-like behaviors, cognitive processes and the nicotine-induced behavioral sensitization as well as processes connected with induction of oxidative stress in the brain of male Swiss mice. The results revealed that co-administration of subthreshold doses of mephedrone and nicotine (0.05 mg/kg each) exerted marked anxiogenic profile in the elevated plus maze and displayed pro-cognitive action in the passive avoidance paradigm (nicotine 0.05 mg/kg and mephedrone 2.5 mg/kg). Furthermore, one of the main findings of the present study was that mephedrone, administered alone at the dose not affecting locomotor activity of mice (1 mg/kg), enhanced the expression of nicotine-induced locomotor sensitization. Moreover, mephedrone administered with nicotine decreased general antioxidant status and catalase activity as well as antioxidant enzymes activity in the hippocampus and prefrontal cortex and increased concentration of malondialdehyde, an indicator of lipid peroxidation processes. Considering the likelihood that mephedrone is taken as a part of polydrug combination with nicotine, the effects of this combination on mammalian organisms have been confirmed in our study. Understanding the consequences of co-administration of psychoactive substances on the central nervous system and oxidative processes in the brain provide the important toxicological significance, and may be useful in polydrug intoxication treatment.

The significance of matrix metalloproteinase (MMP)-2 and MMP-9 in the ischemic stroke.

There is a continuous urgent need to explore the pathogenesis and biochemical changes within the infarcted area during acute ischemic stroke (IS). Matrix metalloproteinases (MMPs), prevailing extracellular endopeptideses, can digest proteins located extracellulary, e.g. collagen, proteoglycans, elastin or fibronectin. Among MMPs, gelatinases (MMP-2 and MMP-9) are the most investigated enzymes. Gelatinases possess the ability to active numerous pro-inflammatory agents as chemokine CXCL-8, interleukin 1ß or tumor necrosis factor α. Moreover, due to digestion of collagen type IV (the component of basal membranes) and tight junction proteins (TJPs) they facilitate to cross the endothelium by leukocytes. Due to the significant role of gelatinases during brain ischemia, their selective inhibition seems to be an interesting kind of treatment of acute stroke. The synthetic inhibitors of gelatineses decrease the infarct volume in animal models of IS. In clinical practice statins, the lipid-lowering drugs possess the ability to inhibit the activity of MMP-9 during acute IS. This review briefly provides the most important information about the involvement of MMP-2 and MMP-9 in the pathogenesis of brain ischemia.

Role of MMP-2 and MMP-9 and their natural inhibitors in liver fibrosis, chronic pancreatitis and non-specific inflammatory bowel diseases.

BACKGROUND: There is a growing evidence that matrix metalloproteinase (MMP)-2 and MMP-9 (gelatinases) play an important role in the pathogenesis of numerous disorders, especially with inflammatory etiology and extracellular matrix (ECM) remodeling. Despite the fact that gelatinases involve in liver cirrhosis is provided in the literature, their role in the pathogenesis of chronic pancreatitis and non-specific inflammatory bowel diseases is still under investigation. DATA SOURCES: We carried out a PubMed search of English-language articles relevant to the involvement of gelatinases in the pathogenesis of liver fibrosis, pancreatitis, and non-specific inflammatory bowel diseases. RESULTS: The decreased activity of gelatinases, especially MMP-2, is related to the development of liver fibrosis, probably due to the decrease of capability for ECM remodeling. Similar situation can be found in chronic pancreatitis; however, reports on this matter are rare. The presence of non-specific inflammatory bowel diseases results in MMP-9 activity elevation. CONCLUSION: The fluctuation of gelatinases activity during liver fibrosis, chronic pancreatitis and non-specific inflammatory bowel diseases is observed, but the exact role of these enzymes demands further studies.

The rtPA increases MMP-9 activity in serum during ischaemic stroke.

BACKGROUND AND PURPOSE: To find the relationship between rtPA treatment vs. MMP-9 activity, MMP-3, and TIMP-1 serum levels related to patients' neurological status during acute ischaemic stroke (IS). MATERIAL AND METHODS: 35 IS patients were enrolled. 14 of them underwent thrombolytic therapy with Actylise (rtPA group). The serum samples were obtained at 3 time-points for rtPA group (time-point 0: 1st-4th hour of stroke; time-point 1 - immediately after rtPA administration; time-point 2 - on day 5-7 from stroke onset). Remaining patients had venous blood collection at two time-points: time-point 1 - 5th-10th hour of stroke and time-point 2 - on day 5-7 of stroke. MMP-9 was analyzed with gelatin zymography, MMP-3 and TIMP-1 serum levels were analyzed with ELISA method. NIHSS improvement ratio (IR) was calculated as a difference between NIHSS score at the admission and discharge of patient. RESULTS: The active form of MMP-9 (86kDa) was not observed in any analyzed samples. Total MMP-9 activity was significantly elevated at time-point 1 in rtPA group in comparison with non-rtPA group. MMP-3 serum level significantly decreased during rtPA administration in comparison with non-rtPA group and it was restored at time-point 2. MMP-3 negatively correlated with IR values (p=0.06). CONCLUSIONS: Thrombolysis applied for IS treatment increases MMP-9 activity in serum, however, rtPA does not facilitate the conversion of pro-MMP-9 into the active form. Our results also suggest the involvement of MMP-3 to the biochemical processes occurring during acute phase of IS.

Can cannabidiol have an analgesic effect?

BACKGROUND: Cannabis, more commonly known as marijuana or hemp, has been used for centuries to treat various conditions. Cannabis contains two main components cannabidiol (CBD) and tetrahydrocannabinol (THC). CBD, unlike THC, is devoid of psychoactive effects and is well tolerated by the human body but has no direct effect on the receptors of the endocannabid system, despite the lack of action on the receptors of the endocannabid system. OBJECTIVES AND METHODS: We have prepared a literature review based on the latest available literature regarding the analgesic effects of CBD. CBD has a wide range of effects on the human body. In this study, we will present the potential mechanisms responsible for the analgesic effect of CBD. To the best of our knowledge, this is the first review to explore the analgesic mechanisms of CBD. RESULTS AND CONCLUSION: The analgesic effect of CBD is complex and still being researched. CBD models the perception of pain by acting on G protein-coupled receptors. Another group of receptors that CBD acts on are serotonergic receptors. The effect of CBD on an enzyme of potential importance in the production of inflammatory factors such as cyclooxygenases and lipoxygenases has also been confirmed. The presented potential mechanisms of CBD's analgesic effect are currently being extensively studied.

Can cannabidiol (CBD) help with low back pain?

INTRODUCTION AND OBJECTIVE: Low back pain (LBP) is a major cause of disability and the main reason why individual patients need medical attention. Pharmacological treatment options for LBP are limited and are often associated with serious side-effects. This makes it necessary to search for new painkillers. One potential therapeutic agent is cannabidiol (CDB). Cannabidiol and tetrahydrocannabinol are the most researched components of cannabis, the plant more commonly known as marijuana or hemp. To the best of our knowledge, this is the first narrative review of the effects of CBD alone on acute and chronic back pain. REVIEW METHODS: Based on the guidelines provided by the Primary Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA), the PubMed/ MEDLINE database was used to identify articles for analysis from the last 30 years. Due to the limited number of studies on this topic, all types of studies that met the inclusion criteria were included. After analysis, 10 studies were included in this review. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: Currently, the use of medical marijuana continues to increase and the Food and Drug Administration (FDA) has already approved four cannabis-based drugs. Cannabidiol (CBD) is a relatively safe substance for humans and generally well tolerated. It is a substance that is easily available and often taken by patients with LBP. SUMMARY: Evidence for the effectiveness of CBD in the treatment of acute low back pain is lacking. There was only one clinical trial conducted in the Emergency Department that showed no superiority of CBD over placebo in acute LBP. The majority of studies concern chronic rather than acute LBP. Although most of the results suggest a beneficial effect of cannabinoids in relieving chronic LBP, hard evidence is lacking. Rigorous randomized controlled trials are needed.

Can Bee Venom Be Used as Anticancer Agent in Modern Medicine?

Honey bee venom in its composition contains many biologically active peptides and enzymes that are effective in the fight against diseases of various etiologies. The history of the use of bee venom for medicinal purposes dates back thousands of years. There are many reports in the literature on the pharmacological properties of bee venom and/or its main components, e.g., anti-arthritic, anti-inflammatory, anti-microbial or neuroprotective properties. In addition, both crude venom and melittin exhibit cytotoxic activity against a wide range of tumor cells, with significant anti-metastatic activity in pre-clinical studies. Due to the constantly increasing incidence of cancer, the development of new therapeutic strategies in oncology is a particular challenge for modern medicine. A review paper discusses the various properties of bee venom with an emphasis on its anticancer properties. For this purpose, the PubMed database was searched, and publications related to "bee", "venom", "cancer" from the last 10 years were selected.

Melanin-The Éminence Grise of Melanoma and Parkinson's Disease Development.

A common feature of Parkinson's disease (PD) and melanoma is their starting points being based on cells capable of converting tyrosine into melanin. Melanocytes produce two types of melanin: eumelanin and pheomelanin. These dyes are designed to protect epidermal cells from the harmful effects of UV radiation. Neurones of the substantia nigra, which degenerate during PD, produce neuromelanin, the physiological role of which is not fully explained. This article discusses the potential role of melanins in the pathogenesis of both diseases. Melanins, due to their ability to accumulate toxic substances, may become their sources over time. The use of glutathione for the synthesis of pheomelanins and neuromelanins may reduce the antioxidant capacity of cells, leading to an excessive synthesis of free radicals. This study also tested the hypothesis that certain drugs used in the treatment of PD (L-DOPA, MAO-B and COMT inhibitors, and amantadine), aimed at increasing dopamine concentration, could potentially contribute to the development of melanoma. The role and properties of melanins should continue to be researched. Whether excessive melanin synthesis or its accumulation in the extracellular space may be factors initiating the development of diseases remains an open question.