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Biomedicines Jun 2024A complication of diabetes is neuropathic pain, which is difficult to control with medication. We have confirmed that neuropathic pain due to mechanical allodynia in...
A complication of diabetes is neuropathic pain, which is difficult to control with medication. We have confirmed that neuropathic pain due to mechanical allodynia in diabetic mice is mediated by a characteristic neuropeptide in the spinal cord. We evaluated the strength of mechanical allodynia in mice using von Frey filaments. When mice were intravenously injected with streptozotocin, mechanical allodynia appeared 3 days later. Antibodies of representative neuropeptides were intrathecally (i.t.) administered to allodynia-induced mice 7 days after the intravenous administration of streptozotocin, and allodynia was reduced by anti-cholecystokinin octapeptide antibodies, anti-nociceptin/orphanin FQ antibodies, and anti-hemokinin-1 antibodies. In contrast, i.t.-administered anti-substance P antibodies, anti-somatostatin antibodies, and anti-angiotensin II antibodies did not affect streptozotocin-induced diabetic allodynia mice. Mechanical allodynia was attenuated by the i.t. administration of CCK-B receptor antagonists and ORL-1 receptor antagonists. The mRNA level of CCK-B receptors in streptozotocin-induced diabetic allodynia mice increased in the spinal cord, but not in the dorsal root ganglion. These results indicate that diabetic allodynia is caused by cholecystokinin octapeptide, nociceptin/orphanin FQ, and hemokinin-1 released from primary afferent neurons in the spinal cord that transmit pain to the brain via the spinal dorsal horn.
PubMed: 38927539
DOI: 10.3390/biomedicines12061332 -
Biomedicines Jun 2024Playing a key role in the organization of striatal motor output, the dopamine (DA)-ergic system regulates both innate and complex learned behaviors. Growing evidence...
Playing a key role in the organization of striatal motor output, the dopamine (DA)-ergic system regulates both innate and complex learned behaviors. Growing evidence clearly indicates the involvement of the DA-ergic system in different forms of repetitive (perseverative) behavior. Some of these behaviors accompany such disorders as obsessive-compulsive disorder (OCD), Tourette's syndrome, schizophrenia, and addiction. In this study, we have traced how the inflexibility of repetitive reactions in the recently developed animal model of hyper-DA-ergia, dopamine transporter knockout rats (DAT-KO rats), affects the realization of innate behavior (grooming) and the learning of spatial (learning and reversal learning in T-maze) and non-spatial (extinction of operant reaction) tasks. We found that the microstructure of grooming in DAT-KO rats significantly differed in comparison to control rats. DAT-KO rats more often demonstrated a fixed syntactic chain, making fewer errors and very rarely missing the chain steps in comparison to control rats. DAT-KO rats' behavior during inter-grooming intervals was completely different to the control animals. During learning and reversal learning in the T-maze, DAT-KO rats displayed pronounced patterns of hyperactivity and perseverative (stereotypical) activity, which led to worse learning and a worse performance of the task. Most of the DAT-KO rats could not properly learn the behavioral task in question. During re-learning, DAT-KO rats demonstrated rigid perseverative activity even in the absence of any reinforcement. In operant tasks, the mutant rats demonstrated poor extinction of operant lever pressing: they continued to perform lever presses despite no there being reinforcement. Our results suggest that abnormally elevated DA levels may be responsible for behavioral rigidity. It is conceivable that this phenomenon in DAT-KO rats reflects some of the behavioral traits observed in clinical conditions associated with endogenous or exogenous hyper-DA-ergia, such as schizophrenia, substance abuse, OCD, patients with Parkinson disease treated with DA mimetics, etc. Thus, DAT-KO rats may be a valuable behavioral model in the search for new pharmacological approaches to treat such illnesses.
PubMed: 38927477
DOI: 10.3390/biomedicines12061270 -
Biomedicines May 2024The escalating rates of morbidity and mortality associated with opioid use disorder (OUD) have spurred a critical need for improved treatment outcomes. This study aimed...
The escalating rates of morbidity and mortality associated with opioid use disorder (OUD) have spurred a critical need for improved treatment outcomes. This study aimed to investigate the impact of prolonged exposure to Fentanyl, a potent opioid, on behavior, biochemical markers, oxidative stress, and the composition of the gut microbiome. Additionally, we sought to explore the therapeutic potential of in mitigating the adverse effects of Fentanyl withdrawal. The study unveiled that chronic Fentanyl administration induced a withdrawal syndrome characterized by elevated cortisol levels (12.09 mg/mL, compared to 6.3 mg/mL for the control group). This was accompanied by heightened anxiety, indicated by a reduction in time spent and entries made into the open arm in the Elevated Plus Maze Test, as well as depressive-like behaviors, manifested through increased immobility time in the Forced Swim Test. Additionally, Fentanyl exposure correlated with decreased gut microbiome density and diversity, coupled with heightened oxidative stress levels, evidenced by elevated malondialdehyde (MDA) and reduced levels of catalase (CAT) and superoxide dismutase (SOD). However, both post- and co-administration of exhibited substantial improvements in these adverse effects, effectively alleviating symptoms associated with OUD withdrawal syndrome and eliciting positive influences on gut microbiota. In conclusion, this research underscores the therapeutic potential of in managing Fentanyl withdrawal symptoms. The findings indicate promising effects in alleviating behavioral impairments, reducing stress, restoring gut microbiota, and mitigating oxidative stress, offering valuable insights for addressing the challenges of OUD treatment.
PubMed: 38927359
DOI: 10.3390/biomedicines12061152 -
Antibiotics (Basel, Switzerland) Jun 2024The long-term stability of antibiotics in culture media remains underexplored in scientific literature. This study evaluated the stability of eight distinct antibiotic...
The long-term stability of antibiotics in culture media remains underexplored in scientific literature. This study evaluated the stability of eight distinct antibiotic stock solutions-amoxicillin, cefotaxime, neomycin, oxytetracycline, florfenicol, enrofloxacin, colistin, and potentiated sulfonamide-and their 10-fold dilution series in tryptone soy broth (TSB) at 37 °C, over 12 days. Samples were collected immediately after preparation and on days 1, 2, 5, 7, 9, and 12, with active substance concentrations measured using ultra-high-performance liquid chromatography (UHPLC) coupled with mass spectrometry. The results indicated that among the ultrapure water stock solutions, neomycin, florfenicol, and potentiated sulfonamide maintained stability (>95%). Within the culture medium, florfenicol showed consistent stability (100%) throughout the study, potentiated sulfonamide experienced minor degradation (>85%), and neomycin underwent significant degradation. Amoxicillin, oxytetracycline, and colistin displayed considerable degradation in both solution types but were more stable in ultrapure water solutions. The stability of cefotaxime and enrofloxacin in ultrapure water solutions and in the medium was very similar when compared; however, 3.6% of the former and 88.7% of the latter remained detectable by day 12. These findings are crucial for minimum inhibitory concentration (MIC) assessments, especially in minimum bactericidal concentration (MBC) studies, and in experiments concerning long-term evolution and co-selection. This study underscores the necessity of stability assessments in culture media to validate future experimental outcomes.
PubMed: 38927215
DOI: 10.3390/antibiotics13060549 -
Scientific Reports Jun 2024Classic psychedelics and MDMA have a colorful history of recreational use, and both have recently been re-evaluated as tools for the treatment of psychiatric disorders.... (Meta-Analysis)
Meta-Analysis
Classic psychedelics and MDMA have a colorful history of recreational use, and both have recently been re-evaluated as tools for the treatment of psychiatric disorders. Several studies have been carried out to assess potential long-term effects of a regular use on cognition, delivering distinct results for psychedelics and MDMA. However, to date knowledge is scarce on cognitive performance during acute effects of those substances. In this systematic review and meta-analysis, we investigate how cognitive functioning is affected by psychedelics and MDMA during the acute drug effects and the sub-acute ("afterglow") window. Our quantitative analyses suggest that acute cognitive performance is differentially affected by psychedelics when compared to MDMA: psychedelics impair attention and executive function, whereas MDMA primarily affects memory, leaving executive functions and attention unaffected. Our qualitative analyses reveal that executive functioning and creativity may be increased during a window of at least 24 h after the acute effects of psychedelics have subsided, whereas no such results have been observed for MDMA. Our findings may contribute to inform recommendations on harm reduction for recreational settings and to help fostering differential approaches for the use of psychedelics and MDMA within a therapeutic framework.
Topics: Humans; Hallucinogens; N-Methyl-3,4-methylenedioxyamphetamine; Cognition; Executive Function; Attention; Memory
PubMed: 38926480
DOI: 10.1038/s41598-024-65391-9 -
Scientific Reports Jun 2024The spontaneous plant landscape is a key focus in the development of urban environments. While many spontaneous plants can coexist with bryophytes to create appealing...
The spontaneous plant landscape is a key focus in the development of urban environments. While many spontaneous plants can coexist with bryophytes to create appealing wilderness landscapes, the potential allelopathic effects of bryophytes on the growth of neighboring spontaneous plants remain uncertain. This study evaluated the allelopathic impact of Thuidium kanedae aqueous extracts on the germination and seedling growth of prevalent urban spontaneous plants by analyzing seed germination, seedling growth morphology, and associated indices. We also investigated the allelopathic potential of the predominant compounds in the extract on seed germination. Our findings reveal that the aqueous extract significantly impeded the seed germination of Ophiopogon japonicus, Taraxacum mongolicum, and Viola philippica, with the level of inhibition correlating positively with concentration. In contrast, Senecio scandens seed germination showed a concentration-dependent reaction, with low concentrations promoting and high concentrations hindering germination. The extract consistently reduced root length in all four species, yet it appeared to increase root vigor. The chlorophyll content in O. japonicus and V. philippica seedlings reached a maximum at a concentration of 5 g/L and decreased with higher extract concentrations. The treatment resulted in elevated catalase and soluble protein levels in the seedlings, indicating that the extract induced stress and enhanced the stress resistance index. L-phenylalanine and 2-phenylethanol, substances present in the extract, were notably inhibitory to seed germination across all species, except for O. japonicus. Notably, 2-phenylethanol exhibited a stronger allelopathic effect than L-phenylalanine. Allelopathy synthetical effect evaluation showed that high concentration of aqueous extract allelopathic inhibition effect on seed germination of four plant species, but allelopathic promotion effect on physiological and biochemical growth of Taraxacum mongolicum, Senecio scandens and Viola philippica. In summary, the study demonstrates that bryophytes exert allelopathic effects on neighboring spontaneous plants, with the degree of influence varying among species. This suggests that the germination and growth of spontaneous plant seeds may be selective in bryophyte-dominated habitats and that the density of bryophytes could shape the evolution of these landscapes.
Topics: Germination; Allelopathy; Seedlings; Plant Extracts; Seeds; Taraxacum; Pheromones; Senecio; Chlorophyll; Phenylalanine; Plant Roots
PubMed: 38926472
DOI: 10.1038/s41598-024-65660-7 -
Bioresources and Bioprocessing Jun 2024Currently, several studies have demonstrated the benefits of medicinal plants in managing type 2 diabetes. In this work, we evaluated the beneficial effects of the...
Currently, several studies have demonstrated the benefits of medicinal plants in managing type 2 diabetes. In this work, we evaluated the beneficial effects of the polyphenolic extract (PESB) from Salvia blancoana subsp. mesatlantica in the management of hypercaloric-feeding and small-dose alloxan-brought type 2 diabetes in rats. We analyzed the chemical constituents of the extract, including flavones and flavonols content, to understand its biological action. The antioxidant activities were evaluated by total antioxidant action, scavenging effect of the free radical DPPH, and reducing power. The obtained results showed that the value of TFC was estimated at 31.90 ± 0.34 mgEQ/g in the PESB extract. The total antioxidant capacity was estimated at 593.51 ± 4.09 mg (EAA)/g, the value of DPPH IC was 7.3 ± 0.00 μg/mL, and the value of EC of reducing power was estimated at 6.43 ± 0.01 μg/mL. In total, 14 phenolic compounds were identified and the naringin was the most dominant (63.19%) while the vanillin was the less recorded (0.10%). Serum glucose decreased significantly (p < 0.05) in rats given PESB (100 mg/kg) after four weeks. Glibenclamide (GLB) and PESB reduced HbA1c and increased plasma insulin in diabetic rats, restoring HOMA-β and HOMA-IR levels to near-normal. Additionally, diabetic rats treated with GLB or PESB showed statistically equivalent results to those of non-diabetic rats regarding hepatic enzymes, renal and lipid markers, as well as cardiovascular indices. The weight loss was significantly lower in diabetic rats receiving a dose of PESB (100 mg/kg), and GLB compared to corresponding untreated diabetic rats (p < 0.01). PESB and GLB showed a prominent protective function in the pancreas, liver, and kidney tissues. This investigation demonstrates the capacity of extracts from leaves of S. blancoana subsp. mesatlantica to manage diabetes mellitus due to their richness in a wide range of bioactive compounds. Therefore, more investigations are required to estimate the safety of the plant use.
PubMed: 38926327
DOI: 10.1186/s40643-024-00769-1 -
Cell Biochemistry and Function Jun 2024Currently, challenges such as chemotherapy resistance, resulting from preoperative and postoperative chemotherapy, postoperative recurrence, and poor bone regeneration... (Review)
Review
Currently, challenges such as chemotherapy resistance, resulting from preoperative and postoperative chemotherapy, postoperative recurrence, and poor bone regeneration quality, are becoming increasingly prominent in osteosarcoma (OS) treatment. There is an urgent need to find more effective ways to address these issues. Ferroptosis is a novel form of iron-dependent programmed cell death, distinct from other forms of cell death. In this paper, we summarize how, through the three major defense systems of ferroptosis, not only can substances from traditional Chinese medicine, antitumor drugs, and nano-drug carriers induce ferroptosis in OS cells, but they can also be combined with immunotherapy, differentiation therapy, and other treatment modalities to significantly enhance chemotherapy sensitivity and inhibit tumor growth. Thus, ferroptosis holds great potential in treating OS, offering more choices and possibilities for future clinical interventions.
Topics: Ferroptosis; Osteosarcoma; Humans; Bone Neoplasms; Antineoplastic Agents; Immunotherapy; Animals
PubMed: 38924104
DOI: 10.1002/cbf.4080 -
Cannabis and Cannabinoid Research Jun 2024Cannabis is one of the world's most commonly used substances; however, many questions remain unanswered as to how cannabis impacts the body. Recently, there has been a...
Acute Cannabis Administration Transiently Reduces Mitochondrial DNA in Young Adults: Findings from a Secondary Analysis of a Double-Blind, Placebo-Controlled, Randomized Clinical Trial.
Cannabis is one of the world's most commonly used substances; however, many questions remain unanswered as to how cannabis impacts the body. Recently, there has been a resurgence of research into the effects of plant-derived cannabinoids on mitochondrial health. In particular, a number of studies implicate mitochondrial-Δ9-tetrahydrocannabinol (Δ9-THC) interactions with altered memory, metabolism, and catalepsy in mice. Although the research in this field is expanding rapidly, there is little known about the effects of cannabis on mitochondria health in human subjects either in acute or chronic term use. Blood samples were obtained from a double-blind, placebo-controlled, parallel-group randomized clinical trial in which adults who regularly use cannabis (1-4 days/week) aged 19-25 years were randomized 2:1 to receive either an active (12.5% Δ9-THC) cigarette or placebo (<0.01% Δ9-THC) cigarette containing 750 mg of cannabis before driving simulator testing. DNA was extracted from whole blood using commercial spin columns, followed by measurement of mt-ND1, mt-ND4, and β2M using quantitative polymerase chain reaction. One-way repeated measures analysis of variance (ANOVA) followed by Dunnett's multiple comparisons test was used to observe changes in mitochondrial DNA (mtDNA) copy number over time. A two-tailed Pearsons R test was used to assess correlations between mtDNA copy number and cannabinoid levels (Δ9-THC and metabolites) in blood. We found that exposure to active cannabis containing Δ9-THC, as opposed to placebo, was associated with an acute reduction in mitochondrial DNA copy number in whole blood at 15 min and 1 h after smoking. The observed decrease in mtDNA copy number negatively correlated with blood concentrations of 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), the two primary metabolites of Δ9-THC, but not Δ9-THC itself. Further, the negative correlation between 11-OH THC and THC-COOH concentrations and mtDNA copy number was found in only a subgroup of participants who use cannabis infrequently, suggesting a tolerance effect. These results illuminate mitochondrial alterations attributed to Δ9-THC consumption, which may be mediated by metabolites. These results appear to suggest stronger effects in individuals who consume cannabis less frequently, suggesting some form of tolerance to the effects of Δ9-THC and its metabolites on mtDNA content in whole blood. Mitochondria; mtDNA; cannabis; THC; THC metabolites; blood; THC-COOH; 11-OH-THC.
PubMed: 38923954
DOI: 10.1089/can.2023.0282 -
Biomedical Chromatography : BMC Jun 2024Abnormal relaxation and contraction of intestinal smooth muscle can cause various intestinal diseases. Diarrhea is a common and important public health problem worldwide...
Revealing the material basis and mechanism for the inhibition of intestinal peristalsis by Zingiber officinale Roscoe through integrated metabolomics, serum pharmacochemistry, and network pharmacology.
Abnormal relaxation and contraction of intestinal smooth muscle can cause various intestinal diseases. Diarrhea is a common and important public health problem worldwide in epidemiology. Zingiber officinale Roscoe (fresh ginger) has been found to treat diarrhea, but the material basis and mechanism of action that inhibits intestinal peristalsis remain unclear. Metabolomics and serum pharmacology were used to identify differential metabolites, metabolic pathways, and pharmacodynamic substances, and were then combined with network pharmacology to explore the potential targets of ginger that inhibit intestinal peristalsis during diarrhea treatment, and the targets identified were verified using molecular docking and molecular dynamic simulation. We found that 25 active components of ginger (the six most relevant components), 35 potential key targets (three core targets), 40 differential metabolites (four key metabolites), and four major metabolic pathways were involved in the process by which ginger inhibits intestinal peristalsis during diarrhea treatment. This study reveals the complex mechanism of action and pharmacodynamic material basis of ginger in the inhibition of intestinal peristalsis, and this information helps in the development of new Chinese medicine to treat diarrhea and lays the foundation for the clinical application of ginger.
PubMed: 38922712
DOI: 10.1002/bmc.5932