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Clinical, Cosmetic and Investigational... 2024Rosacea is a chronic inflammatory skin disease that affects a patient's appearance and quality of life. It mainly affects the midface region and presents as erythema,... (Review)
Review
Rosacea is a chronic inflammatory skin disease that affects a patient's appearance and quality of life. It mainly affects the midface region and presents as erythema, flushing, telangiectasia, papules, pustules, and rhinophyma. Despite its prevalence, the precise pathophysiology of rosacea remains unknown, and novel pharmacological therapies are currently under investigation. Tranexamic acid (TA) is a synthetic, lysine-like compound that competitively inhibits fibrinogen production by synthesizing fibrinolytic enzymes. In addition to its popular application in hemorrhage treatment, TA has been used to manage a number of skin conditions, including melasma, chronic urticaria, and angioedema. TA is a better option for melasma treatment. However, the role of TA in treating rosacea has not yet been systematically elucidated. In this study, we reviewed all available literature on the use of TA for rosacea treatment. The included articles examined the therapeutic effects of TA in patients with rosacea, including traditional methods such as oral and topical administration and more novel approaches such as intradermal injections, microneedling, and laser-assisted delivery. Several recent clinical studies demonstrated that TA alleviates rosacea symptoms by restoring the permeability barrier, ameliorating the immune reaction, and inhibiting angiogenesis. In this review, we summarized the function and potential application of TA in rosacea treatment, aiming to facilitate the implementation of clinical applications.
PubMed: 38895607
DOI: 10.2147/CCID.S473598 -
Journal of Clinical Medicine May 2024Sedentary lifestyles, work overload, and lack of regular physical activity are risk factors for spinal pain syndrome. In everyday medical practice, spinal pain syndrome... (Review)
Review
Sedentary lifestyles, work overload, and lack of regular physical activity are risk factors for spinal pain syndrome. In everyday medical practice, spinal pain syndrome of a muscular or myofascial, or non-neurogenic, nature is diagnosed. This problem affects a large group of patients and reaches about 70-80% of spinal pain cases. Usually, one of the primary treatments is with NSAIDs (Non-steroidal Anti-Inflammatory Drugs). In this case, one treatment method that is safe and has no side effects is spinal mesotherapy. This method consists of performing multi-point intradermal microinjections with the administration of drugs or medical devices. Based on a new perspective on the treatment of spinal pathology-the so-called three-stage treatment concept-it is necessary to deal with the risk factor(s) of spinal pain syndrome and reduce or at least modify them (stage I). This is followed by a broadly understood medical therapy, in this case spinal mesotherapy (stage II), which aims to relax tense tissues, improve mobility in the spine and thus reduce pain. As a result, conditions are created for the necessary process, which is rehabilitation in the broadest sense (stage III). Movement therapy, which is crucial in spinal pain syndrome, is performed with less pain, after obtaining better patient mobility. The purpose of this article is to evaluate the role of rehabilitation of patients after spinal mesotherapy in terms of the three-stage treatment concept for spinal pathology.
PubMed: 38892905
DOI: 10.3390/jcm13113195 -
Journal of Molecular Neuroscience : MN Jun 2024Binge drinking causes a range of problems especially damage to the nervous system, and the specific neural mechanism of brain loss and behavioral abnormalities caused by...
Binge drinking causes a range of problems especially damage to the nervous system, and the specific neural mechanism of brain loss and behavioral abnormalities caused by which is still unclear. Extracellular regulated protein kinases (ERK) maintain neuronal survival, growth, and regulation of synaptic plasticity by phosphorylating specific transcription factors to regulate expression of brain-derived neurotrophic factor (BDNF). Dual-specific phosphatase 1 (DUSP1) and DUSP6 dephosphorylate tyrosine and serine/threonine residues in ERK1/2 to inactivate them. To investigate the molecular mechanism by which alcohol affects memory and emotion, a chronic intermittent alcohol exposure (CIAE) model was established. The results demonstrated that mice in the CIAE group developed short-term recognition memory impairment and anxiety-like behavior; meanwhile, the expression of DUSP1 and DUSP66 in the mPFC was increased, while the levels of p-ERK and BDNF were decreased. Micro-injection of DUSP1/6 inhibitor BCI into the medial prefrontal cortex (mPFC) restored the dendritic morphology by reversing the activity of ERK-BDNF and ultimately improved cognitive and emotional impairment caused by CIAE. These findings indicate that CIAE inhibits ERK-BDNF by increasing DUSP1/6 in the mPFC that may be associated with cognitive and emotional deficits. Consequently, DUSP1 and DUSP6 appear to be potential targets for the treatment of alcoholic brain disorders.
Topics: Animals; Brain-Derived Neurotrophic Factor; Mice; Male; Mice, Inbred C57BL; Dual Specificity Phosphatase 1; Prefrontal Cortex; Ethanol; Dual Specificity Phosphatase 6; Aminoacetonitrile; Anxiety; MAP Kinase Signaling System
PubMed: 38890235
DOI: 10.1007/s12031-024-02237-z -
Journal of Pharmacy & Bioallied Sciences Apr 2024Mesotherapy is a popular novel therapeutic modality that delivers intradermal or subcutaneous microinjections of pharmaceutical compounds. Although this novel treatment... (Review)
Review
Mesotherapy is a popular novel therapeutic modality that delivers intradermal or subcutaneous microinjections of pharmaceutical compounds. Although this novel treatment method is used commonly in aesthetic dermatology, there is little information about the details of injections, efficacy, and side effects of mesotherapy in melasma. In this review, we evaluated the efficacy of various types of anti-pigmentation agents used with mesotherapy in the management of melasma.
PubMed: 38882767
DOI: 10.4103/jpbs.jpbs_1192_23 -
Experimental Neurology Jun 2024Pain in Parkinson's disease (PD) has been validated as one of the major non-motor dysfunctions affecting the quality of life and subsequent rehabilitation. In the...
Antinociceptive role of the thalamic dopamine D3 receptor in descending modulation of intramuscular formalin-induced muscle nociception in a rat model of Parkinson's disease.
Pain in Parkinson's disease (PD) has been validated as one of the major non-motor dysfunctions affecting the quality of life and subsequent rehabilitation. In the present study, we investigated the role of the dopamine D3 receptor in the thalamic mediodorsal (MD) and ventromedial (VM) nuclei mediated descending control of nociception and intramuscular (i.m.) 2.5% formalin-induced persistent muscle nociception. Paw withdrawal reflexes were measured in naive rats and rats subjected to PD induced by unilateral microinjection of 6 μg 6-OHDA into the rat striatum. Formalin-induced muscle nociception in phase 1, inter-phase, and phase 2 was significantly greater in PD rats compared to naive and vehicle-treated rats (P ˂ 0.001). PD rats exhibited bilaterally mechanical hyperalgesia and heat hypoalgesia in formalin-induced muscle nociception. Microinjection of SK609, a dopamine D3 receptor agonist, at various doses (2.5-7.5 nmol/0.5 μl) into the thalamic VM nucleus dose-dependently prolonged heat-evoked paw withdrawal latencies in both naive and PD rats. Administration of SK609 to either the MD or VM nuclei had no effect on noxious mechanically evoked paw withdrawal reflexes. Pre-treatment of the thalamic MD nucleus with SK609 significantly attenuated formalin-induced nociception, and reversed mechanical hyperalgesia, but not heat hypoalgesia. Pre-treatment of the thalamic VM nucleus with SK609 inhibited formalin-induced nociception in the late phase of phase 2 (30-75 min) and heat hypoalgesia, but not mechanical hyperalgesia (P < 0.05). It is suggested that the dopamine D3 receptors in the thalamus play an antinociceptive role in the descending modulation of nociception. Activation of D3 receptors within the thalamic MD and VM nuclei attenuates descending facilitation and enhances descending inhibition in rats during PD.
PubMed: 38879111
DOI: 10.1016/j.expneurol.2024.114846 -
PLoS Genetics Jun 2024Tardigrades are small aquatic invertebrates known for their remarkable tolerance to diverse extreme stresses. To elucidate the in vivo mechanisms underlying this...
Tardigrades are small aquatic invertebrates known for their remarkable tolerance to diverse extreme stresses. To elucidate the in vivo mechanisms underlying this extraordinary resilience, methods for genetically manipulating tardigrades have long been desired. Despite our prior success in somatic cell gene editing by microinjecting Cas9 ribonucleoproteins (RNPs) into the body cavity of tardigrades, the generation of gene-edited individuals remained elusive. In this study, employing an extremotolerant parthenogenetic tardigrade species, Ramazzottius varieornatus, we established conditions that led to the generation of gene-edited tardigrade individuals. Drawing inspiration from the direct parental CRISPR (DIPA-CRISPR) technique employed in several insects, we simply injected a concentrated Cas9 RNP solution into the body cavity of parental females shortly before their initial oviposition. This approach yielded gene-edited G0 progeny. Notably, only a single allele was predominantly detected at the target locus for each G0 individual, indicative of homozygous mutations. By co-injecting single-stranded oligodeoxynucleotides (ssODNs) with Cas9 RNPs, we achieved the generation of homozygously knocked-in G0 progeny, and these edited alleles were inherited by G1/G2 progeny. This is the first example of heritable gene editing in the entire phylum of Tardigrada. This establishment of a straightforward method for generating homozygous knockout/knock-in individuals not only facilitates in vivo analyses of the molecular mechanisms underpinning extreme tolerance, but also opens up avenues for exploring various topics, including Evo-Devo, in tardigrades.
Topics: Animals; Tardigrada; CRISPR-Cas Systems; Gene Editing; Parthenogenesis; Homozygote; Female; Gene Knock-In Techniques; Gene Knockout Techniques; Alleles
PubMed: 38870088
DOI: 10.1371/journal.pgen.1011298 -
Behavioural Pharmacology Jun 2024Acute stress, as a protective mechanism to respond to an aversive stimulus, can often be accompanied by suppressing pain perception via promoting consistent burst firing...
D2-like dopamine receptors blockade within the dentate gyrus shows a greater effect on stress-induced analgesia in the tail-flick test compared to D1-like dopamine receptors.
INTRODUCTION
Acute stress, as a protective mechanism to respond to an aversive stimulus, can often be accompanied by suppressing pain perception via promoting consistent burst firing of dopamine neurons. Besides, sensitive and advanced research techniques led to the recognition of the mesohippocampal dopaminergic terminals, particularly in the hippocampal dentate gyrus (DG). Moreover, previous studies have shown that dopamine receptors within the hippocampal DG play a critical role in induced antinociceptive responses by forced swim stress (FSS) in the presence of inflammatory pain. Since different pain states can trigger various mechanisms and transmitter systems, the present experiments aimed to investigate whether dopaminergic receptors within the DG have the same role in the presence of acute thermal pain.
METHODS
Ninety-seven adult male albino Wistar rats underwent stereotaxic surgery, and a stainless steel guide cannula was unilaterally implanted 1 mm above the DG. Different doses of SCH23390 or sulpiride as D1- and D2-like dopamine receptor antagonists were microinjected into the DG 5-10 min before exposure to FSS, and 5 min after FSS exposure, the tail-flick test evaluated the effect of stress on the nociceptive response at the time-set intervals.
RESULTS
The results demonstrated that exposure to FSS could significantly increase the acute pain perception threshold, while intra-DG administration of SCH23390 and sulpiride reduced the antinociceptive effect of FSS in the tail-flick test.
DISCUSSION
Additionally, it seems the D2-like dopamine receptor within the DG plays a more prominent role in FSS-induced analgesia in the acute pain model.
PubMed: 38869040
DOI: 10.1097/FBP.0000000000000782 -
Life Sciences Jun 2024Malaria is a major public health concern. The development of parasite-based vaccine RTS/AS01 has some therapeutic value but its lower efficacy is one of the major... (Review)
Review
Malaria is a major public health concern. The development of parasite-based vaccine RTS/AS01 has some therapeutic value but its lower efficacy is one of the major limitations. Mosquito-based transmission-blocking vaccines could have a higher potential for parasite inhibition within the mosquitoes. Several genes of mosquito midgut, salivary gland, hemolymph, etc. get activate in response to the Plasmodium-infected blood and helps in parasite invasion directly or indirectly inside the mosquito. The studies of such genes provided a new insight into developing the more efficient vaccines. In the field of malaria genetics research, RNAi has become an innovative strategy used to identify mosquito candidate genes for transmission-blocking vaccines. This review targeted the gene studies that have been conducted in the period 2000-2023 in different malaria vectors against different malarial parasites using the RNAi approach to reveal mosquito novel gene candidates for vaccine development.
PubMed: 38866221
DOI: 10.1016/j.lfs.2024.122822 -
Experimental Neurology Jun 2024Neuroinflammation is a common pathological feature and onset in multiple cognitive disorders, including postoperative cognitive dysfunction (POCD). Iron deposition was...
Neuroinflammation is a common pathological feature and onset in multiple cognitive disorders, including postoperative cognitive dysfunction (POCD). Iron deposition was proved to participate in this process. But how iron mediates inflammation-induced cognitive deficits remains unknown. This study aimed to investigate the mechanism of iron through the neuroprotective effect of the iron chelator deferoxamine (DFO) in a mouse model of lipopolysaccharide (LPS)-induced cognitive impairment. Adult C57BL/6 mice were pretreated with 0.5 μg of DFO three days before intracerebroventricular microinjection of 2 μg of LPS. The mice showed memory deficits by showing decreased percentage of distance and the time within the platform-site quadrant, fewer platform-site crossings, and shortened swimming distance around the platform in the Morris water maze test, which were significantly mitigated by DFO pretreatment. Mechanistically, DFO prevented LPS-induced iron accumulation and modulated the imbalance of proteins expression related to iron metabolism, including elevated transferrin (TF) levels and reduced ferritin (Fth) caused by LPS. DFO attenuated the LPS-induced lipid peroxidation and oxidative stress, which is evidenced by the decrease of malondialdehyde (MDA) and lipid peroxidation (LPO) levels and the increase of superoxide dismutase (SOD) activity and glutathione (GSH) concentration. Moreover, DFO ameliorated ferroptosis-like mitochondrial damages in the hippocampus and also alleviated the expression of ferroptosis-related proteins in the hippocampus. Additionally, DFO attenuated microglial activation, alleviated LPS-induced inflammation, and reduced elevated levels of IL-6 and TNF-α in the hippocampus. Taken together, our findings suggested that DFO exerts neuroprotective effects by alleviating excessive iron participation in lipid peroxidation, reducing the occurrence of ferroptosis, inhibiting the vicious cycle between oxidative stress and inflammation, and ultimately ameliorating LPS-induced cognitive dysfunction, providing novel insights into the immunopathogenesis of inflammation-related cognitive dysfunction and future potential prevention options targeting iron.
PubMed: 38866103
DOI: 10.1016/j.expneurol.2024.114862 -
Insect Science Jun 2024The sweet potato weevil (Cylas formicarius) is a critical pest producing enormous global losses in sweet potato crops. Traditional pest management approaches for sweet...
The sweet potato weevil (Cylas formicarius) is a critical pest producing enormous global losses in sweet potato crops. Traditional pest management approaches for sweet potato weevil, primarily using chemical pesticides, causes pollution, food safety issues, and harming natural enemies. While RNA interference (RNAi) is a promising environmentally friendly approach to pest control, its efficacy in controlling the sweet potato weevil has not been extensively studied. In this study, we selected a potential target for controlling C. formicarius, the Troponin I gene (wupA), which is essential for musculature composition and crucial for fundamental life activities. We determined that wupA is abundantly expressed throughout all developmental stages of the sweet potato weevil. We evaluated the efficiency of double-stranded RNAs in silencing the wupA gene via microinjection and oral feeding of sweet potato weevil larvae at different ages. Our findings demonstrate that both approaches significantly reduced the expression of wupA and produced high mortality. Moreover, the 1st instar larvae administered dswupA exhibited significant growth inhibition. We assessed the toxicity of dswupA on the no-target insect silkworm and assessed its safety. Our study indicates that wupA knockdown can inhibit the growth and development of C. formicarius and offer a potential target gene for environmentally friendly control.
PubMed: 38863245
DOI: 10.1111/1744-7917.13403