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Background and Aims: Klebsiella oxytoca (K. oxytoca) is the second bacterial cause of nosocomial infections in the general population after K. pneumoniae. This study surveyed the frequency of cytotoxin-producing strains of K. oxytoca and their antibiotic susceptibility profile in a cohort of children admitted to a referral hospital with different malignancies. Methods: The Stool samples of children admitted to the Cancer Chemotherapy Unit of the Mofid Children's Hospital, Tehran, Iran were analyzed using conventional biochemical tests and polymerase chain reaction targeting the pehX gene to identify K. oxytoca. The antibiotic susceptibility profile of isolated K. oxytoca against commonly prescribed antibiotics used in treating infection at the facility was determined using the Kirby-Bauer disk diffusion technique. Also, the prevalence of genes encoding toxins among K. oxytoca was identified by PCR assay. Results: The Stool samples of 280 participants were taken for the study of which 38 samples [(55.3% (21/38) 42 males and 44.7% (17/38) females)] tested positive for various Klebsiella spp. Out of this, K. oxytoca was identified in 2.5% (7/280) stools using cultures and conventional biochemical tests. Also, the stools of 2.9% (8/280) of the participants tested positive for K. oxytoca using PCR assay. Using PCR, (2/7) of the K. oxytoca isolates tested positive for the npsA and npsB genes and were identified as toxigenic K. oxytoca strains. Conclusion: The prevalence of toxin-producing K. oxytoca strains in stool samples of children diagnosed with cancer in Iran is relatively low. Most of the K. oxytoca isolates were susceptible to tested antibiotics. Globally, active surveillance of toxigenic K. oxytoca strains in patients with different malignancies or immunocompromised patients is recommended in healthcare settings.
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BACKGROUND: Premature ejaculation (PE) is a common sexual problem, resulting in adverse effects on the quality of life, of both the patient and the partner. The idea of muscular contraction inhibition during the ejection phase of ejaculation by Botulinum toxin-A injection may delay ejaculation. AIM OF STUDY: This study was performed to assess the efficacy and safety of Botulinum toxin-A injection in PE treatment. MATERIAL AND METHODS: This study included 45 married male patients diagnosed with primary PE. All included patients were injected with 75 units of Dysport equal efficacy of 25 units of Botulinum toxin-A (Botox) into three sites: the root of the penis (Group 1), glans penis (Group 2), and each side of the ischiocavernosus muscle (Group 3). All patients were subjected to an assessment of intravaginal ejaculation latency time (IELT) using a stopwatch and answering the Premature Ejaculation Diagnostic Tool (PEDT) Questionnaire before and after treatment. RESULTS: There was a statistically significant improvement in IELT after treatment in all groups. The most significant improvement was shown in Group 3 (average 108% increase), followed by Group 1 (74%) and Group 2 (40%), respectively. There was a positive correlation between age and the improvement in improved IELT. There was a statistically significant improvement in PEDTq scores in Group 1 and Group 3. CONCLUSION: Botulinum toxin-A injection into the root of the penis and ischiocavernosus muscle could be recommended in the treatment of premature ejaculation.
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Enzyme-linked immunosorbent assays (ELISA) are currently the method of choice for the serodiagnosis of pertussis and play a key role in the diagnosis of pertussis in adolescents and adults, as well as in epidemiological studies. In the present study, the in-house developed indirect ELISA was comparatively evaluated with six commercial kits from various manufacturers. Antipertussis antibodies were measured in 40 serum samples from patients with clinical symptoms of respiratory tract infection, in two WHO standards, and in seven human ECDC control sera. IgA and IgG antibodies were detected at a diagnostically significant level by different ELISA kits of 5.0% to 27.0% and 12.0% to 70.0% of patients' sera, appropriately. The analysis of results carried out with six commercial kits showed only 17.5% consistent results in class IgG (either clearly positive or negative). The average percentage of errors in the level of antibodies determined in the control samples, reference serum samples, differed quite significantly and ranged from 9.5% to 35.4% depending on the kit. This poor correlation of the results obtained on various serological tests intended for the serodiagnosis of pertussis may cause very serious diagnostic problems, especially when examining a serum sample obtained once during the course of the disease.
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There are numerous medical and dental disorders for which there are no effective traditional therapy options. For various medical and dental disorders, botulinum toxin (BT) can be employed as an alternate therapeutic option that uses the chemodenervation approach. The range of dentistry treatment choices is expanding quickly. Applications of non-traditional therapy alternatives, such as the use of BT, are becoming more and more common in this situation. Although BT has been shown to be effective in a number of circumstances, its application in esthetic operations, such as the treatment of facial wrinkles, has gained widespread acceptance. This research is especially interested in applications of BT related to dentistry in the craniofacial region. For many diseases that a dentist would be interested in treating, BT provides a temporary, reversible, and generally safe therapy option. Due to their extensive knowledge of the anatomy of the faciomaxillary region, dental surgeons are a potential pool of operators who, with a small amount of skill enhancement, can use BT in their toolkit. This broadens the scope of minimally invasive alternatives to invasive protocols or refractory conditions. An online search was conducted for the use of BT in dentistry; all studies and articles pertaining to the subject were chosen, and dental-related content was removed and summarized. The fundamentals of BT and some of its applications in dentistry are covered in this article. The comprehensive details of its application in dentistry will be covered in the upcoming sections.
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T-2 toxin is recognized as the most potent and prevalent secondary metabolite among monotrichous mycotoxins produced by Fusarium species. Multiple studies have substantiated the hepatotoxic effects of T-2 toxin. This study aimed to investigate whether NF-κB and NLRP3-mediated pyroptosis is involved in the underlying mechanism of T-2 toxin hepatotoxicity. We designed three groups of rat models, blank control; solvent control and T-2 toxin (0.2 mg/kg body weight/day), which were euthanized at week 8 after gavage staining of the toxin. Through HE staining and biochemical indicators associated with liver injury, we observed that T-2 toxin induced liver damage in rats. By Western blot analysis and qRT-PCR, we found that the expression levels of pyroptosis-related genes and proteins were significantly higher in the T-2 toxin group. In addition, we also found a significant increase in the expression of p-NF-κB protein, an upstream regulator of NLRP3. In conclusion, NF-κB and NLRP3-mediated pyroptosis may be involved in the mechanism of hepatotoxic action of T-2 toxin, which provides a new perspective.
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OBJECTIVE: Aim: To study the effectiveness of BTA in a total dose of 100 IU as the preparation for patients with primary and incisional ventral hernias (VH). PATIENTS AND METHODS: Materials and Methods: The prospective study included 59 patients with large VH (defect ³10 cm). All patients received 100 IU of BTA in abdominal wall muscles 4-5 weeks before surgery from June 2017 to December 2022. An average age of the patients was 59.13 ± 9.07 years, body mass index - 32.20 ± 4.95 kg/m2. RESULTS: Results: An average width of the hernia defect after BTA decreased by 4.5 ± 1.11 cm (p<0.001). An average length of the hernia defect after BTA also decreased, without clinical significance. A significant increase in the length of the abdominal wall and a decrease in its thickness were observed. The abdominal cavity volume after BTA increased by 4.04 ± 4.55% (p=0.008) and the hernial sac volume decreased by 21.43 ± 16.57% (p=0.005). All patients underwent surgery with hernia defect suturing and without component separation: laparoscopic IPOM hernioplasty - 50 (84.7%) patients, open IPOM hernia repair - 7 (11.9%) patients, open sublay hernioplasty - 2 (3.4%) patients. There was no recurrence of hernia during 12 months after surgery. CONCLUSION: Conclusions: The administration of 100 IU BTA allows to increase the length of the abdominal wall muscles and to perform laparoscopic IPOM hernioplasty for patients with large VH.
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Toxinas Botulínicas Tipo A , Hérnia Ventral , Herniorrafia , Laparoscopia , Humanos , Pessoa de Meia-Idade , Hérnia Ventral/cirurgia , Masculino , Feminino , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/uso terapêutico , Herniorrafia/métodos , Estudos Prospectivos , Laparoscopia/métodos , Idoso , Músculos Abdominais , Resultado do Tratamento , Parede Abdominal/cirurgia , Hérnia Incisional/cirurgiaRESUMO
BACKGROUND: The pine wood nematode Bursaphelenchus xylophilus, a severe invasive species, is responsible for causing widespread pine wilt disease. The CytCo protein, a pore-forming toxin derived from Conidiobolus obscurus, exhibits nematotoxicity towards B. xylophilus. RESULTS: Our present study reveals the expression variation of a range of gene products in B. xylophilus that respond to the effects of CytCo using the isobaric tags for relative and absolute quantification proteomics technology. Functional enrichment analysis indicates that many differentially expressed proteins are linked to calcium signaling system, proteasome, energy production and conversion, and the determination of adult lifespan. It suggests that the dysregulation of calcium homeostasis, energy metabolism, and apoptosis contribute to the CytCo nematotoxicity. Using the calcium ion (Ca2+)-indicator calcein, we detected changes in Ca2+ levels in B. xylophilus, with a significantly increase in fluorescence in the nematode's intestine and pseudocoelom following CytCo treatments. Meanwhile, the apoptosis and reactive oxygen species (ROS) assays showed an enhancement of fluorescence in B. xylophilus cells, with increased CytCo concentrations. CONCLUSION: The protein toxin CytCo triggers Ca2+ leakage, disrupts Ca2+ balance in B. xylophilus, and induces apoptosis and ROS outburst, thereby intensifying its nematotoxic effects. This finding facilitates our understanding of the modes of action of nematotoxic proteins, and contributes to the development of innovative nematode control strategies. © 2024 Society of Chemical Industry.
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BACKGROUND: Spastic pelvic floor syndrome (SPFS) is a refractory pelvic floor disease characterized by abnormal (uncoordinated) contractions of the external anal sphincter and puborectalis muscle during defecation, resulting in rectal emptation and obstructive constipation. The clinical manifestations of SPFS are mainly characterized by difficult defecation, often accompanied by a sense of anal blockage and drooping. Manual defecation is usually needed during defecation. From physical examination, it is commonly observed that the patient's anal muscle tension is high, and it is difficult or even impossible to enter with his fingers. AIM: To investigate the characteristics of anorectal pressure and botulinum toxin A injection combined with biofeedback in treating pelvic floor muscle spasm syndrome. METHODS: Retrospective analysis of 50 patients diagnosed with pelvic floor spasm syndrome. All patients underwent pelvic floor surface electromyography assessment, anorectal dynamics examination, botulinum toxin type A injection 100 U intramuscular injection, and two cycles of biofeedback therapy. RESULTS: After the botulinum toxin A injection combined with two cycles of biofeedback therapy, the patient's postoperative resting and systolic blood pressure were significantly lower than before surgery (P < 0.05). Moreover, the electromyography index of the patients in the resting stage and post-resting stages was significantly lower than before surgery (P < 0.05). CONCLUSION: Botulinum toxin A injection combined with biofeedback can significantly reduce pelvic floor muscle tension in treating pelvic floor muscle spasm syndrome. Anorectal manometry is an effective method to evaluate the efficacy of treatment objectively. However, randomized controlled trials are needed.
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BACKGROUND: Nasolabial fold (NLF) depression can affect the facial appearance of patients to some extent and increase their psychological burdens. In recent years, autologous fat grafting (AFG) combined with botulinum toxin A (BTX-A) injection (AFG + BTX-A injection) has been gradually applied in the treatment of patients with NLF depression. Although studies have been conducted on the efficacy and safety of AFG + BTX-A injection in treating NLF depression, the experimental design, observational indicators, and sample enrollment criteria vary remarkably, making it difficult to draw convincing and consistent conclusions. Thus, further relevant research is warranted. AIM: To assess the esthetic improvement, efficacy, and safety of AFG + BTX-A injections in patients with NLF depression. METHODS: This study included 60 patients with NLF depression who were treated in our hospital from February 2019 to April 2021. These patients were categorized into control (n = 30) and observation (n = 30) groups. The observation group received AFG + BTX-A injection, whereas the control group underwent AFG only. All patients were evaluated using the wrinkle severity rating scale (WSRS) and global aesthetic improvement scale. The compactness of facial contours, skin evaluation indexes, adverse reactions, and satisfaction of the two groups were evaluated 3 months postoperatively. RESULTS: The WSRS scores of the observation group at 1, 3, and 6 months postoperatively were lower than those of the control group (P < 0.05). Three months postoperatively, facial fine lines and pores showed obvious improvement and the skin index score was higher in the observation group than in the control group (P < 0.05). The compactness of facial contours was better in the observation group than in the control group (P < 0.05). In addition, no remarkable differences were noted in the incidence of postoperative adverse reactions such as facial stiffness, facial asymmetry, facial bruising, and facial concavity inequality (P > 0.05). CONCLUSION: AFG + BTX-A injection is a highly safe, cost-effective, effective, and long-lasting treatment for NLF depression with high esthetic value, which should be promoted in the future.
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The effect of reinforcing and reducing techniques of moxibustion depends on types of moxibustion, operation methods and characteristics of acupoints. According to the ups and downs of pathogenic factors and healthy qi during the occurrence and development of prostate cancer, three stages are divided, namely, the stage of initial accumulation of cancer toxicity, the stage of the deficiency of healthy qi and toxin retention, and the stage of yang deficiency and cold stagnation. In the stage of initial accumulation of cancer toxicity, zangfu function is impaired and the dampness, heat and stasis toxin are accumulated in the body; due to which, the reducing technique of moxibustion should be dominant and the healthy qi be supported in combination. In treatment, the wheat-grain sized cone moxibustion, suppurative moxibustion and garlic-isolated moxibustion are applicable. The reducing purpose of moxibustion is obtained by delivering an appropriate increased number of moxa cones, large dosage and strong stimulation at acupoints. In the stage of the deficiency of healthy qi and toxin retention, qi movement is weakened and cancer toxin consumes yin; the reinforcing healthy qi and removing pathogenic factors should be operated simultaneously. In treatment, mild moxibustion and suppurative moxibustion can be used. The reduced number of moxa cones, moderate dosage of moxibustion and mild stimulation at acupoints should be considered to gently adjust the conditions of deficiency and excess. In the stage of yang deficiency and cold stagnation, spleen and kidney yang is deficient, and the meridians are blocked by cold and damp pathogens. In treatment, the reinforcing technique of moxibustion should be used specially and eliminating pathogenic factors be combined. Monkshood cake-insulated moxibustion, salt-insulated moxibustion and wheat-grain sized cone moxibustion can be adopted. The less number of moxa cones, small dosage and appropriately increased frequency of treatment should be considered to produce the gentle and sustained stimulation at acupoints so as to excite the healthy qi and promote the transformation of qi and blood.
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Moxibustão , Neoplasias da Próstata , Humanos , Moxibustão/métodos , Masculino , Neoplasias da Próstata/terapia , Pontos de AcupunturaRESUMO
Mycobacterium indicus pranii (MIP), a benign saprophyte with potent immunomodulatory attributes, holds a pivotal position in mycobacterial evolution, potentially serving as the precursor to the pathogenic Mycobacterium avium complex (MAC). Despite its established immunotherapeutic efficacy against leprosy and notable outcomes in gram-negative sepsis and COVID-19 cases, the genomic and biochemical features of MIP remain largely elusive. This study explores the uncharted territory of toxin-antitoxin (TA) systems within MIP, hypothesizing their role in mycobacterial pathogenicity regulation. Genome-wide screening, employing diverse databases, unveils putative TA modules in MIP, setting the stage for a comparative analysis with known modules in Mycobacterium tuberculosis, Mycobacterium smegmatis, Escherichia coli, and Vibrio cholerae. The study further delves into the TA network of MAC and Mycobacterium intracellulare, unraveling interactive properties and family characteristics of identified TA modules in MIP. This comprehensive exploration seeks to illuminate the contribution of TA modules in regulating virulence, habitat diversification, and the evolutionary pathogenicity of mycobacteria. The insights garnered from this investigation not only enhance our understanding of MIP's potential as a vaccine candidate but also hold promise in optimizing tuberculosis drug regimens for expedited recovery.
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Ear dyskinesia, also known as "moving ear syndrome," is a rare movement disorder characterized by involuntary, rhythmic, or semi-rhythmic contractions of the external ear muscles. The condition is not well-documented in the medical literature, with only a few case reports available. We present the case of a 37-year-old teacher from Saudi Arabia who developed a history of sudden, progressive involuntary movement of the posterior head region, provoking movement of the external ears, over the course of one year. The movements were non-rhythmical, more prominent on the right side, and associated with occasional involvement of the face and anterior neck muscles. The patient had no history of neuroleptic use or other relevant medical conditions. Examination confirmed the presence of palpable muscle contractions originating mainly from the posterior region, with the movements not synchronized across the two sides. Investigations, including blood tests and brain MRI, did not reveal any underlying pathology. A diagnosis of ear dyskinesia was made, and botulinum toxin treatment was recommended; however, the treatment showed no results, and then the patient was subsequently lost to follow-up. This case adds to the limited literature on the rare phenomenon of ear dyskinesia, highlighting the clinical presentation and the challenges in the management of this unusual movement disorder. Further research is needed to better understand the underlying mechanisms and optimal treatment approaches for this condition.
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Thoracic outlet syndrome (TOS) results from compression of the neurovascular bundle in the thoracic outlet. Several etiologies can contribute to the development of thoracic outlet syndrome, including both congenital and acquired causes. Historically, trapezius pathology has not been considered a cause of TOS; however, here we report a patient with neurogenic TOS plus ipsilateral trapezius hypertonicity and hypertrophy who had significant symptomatic improvement following botulinum toxin injections to trapezius.
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Spider venom is a natural source of diverse biomolecules, but due to technical limitations, only a small fraction has been studied. With the advancement of omics technologies, research on spider venom has broadened, greatly promoting systematic studies of spider venom. Agelena limbata is a common spider found in vegetation, known for constructing funnel-shaped webs, and feeding on insects such as Diptera and Homoptera. However, due to its small size and the difficulty in obtaining venom, the composition of Agelena limbata venom has never been studied. In this study, a transcriptomics approach was used to analyze the toxin components in the venom of Agelena limbata, resulting in the identification of 28 novel toxin-like sequences and 24 peptidases. Based on sequence similarity and differences in cysteine motifs, the 28-novel toxin-like sequences were classified into 10 superfamilies. According to the results annotated in the database, the 24 peptidases were divided into six distinct families, with the serine protease family being the most common. A phylogenetic tree was constructed using the toxin-like sequences of Agelena limbata along with Psechrus triangulus and Hippasa lycosina. An analysis of the structural domains and motifs of Agelena limbata was also conducted. The results indicated that Agelena limbata is more distantly related to the other two species of funnel-web spiders, and that the toxin superfamily IX has a unique function compared to the other superfamilies. This study reveals the components of the Agelena limbata venom, deepening our understanding of it, and through bioinformatics analysis, has identified unique functions of the toxin superfamilies, providing a scientific basis for the development of bioactive drugs in the future.
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BACKGROUND: The traction-induced esophageal growth (Foker) process for the treatment of long gap esophageal atresia (LGEA) relies on applying progressive tension to the esophagus to induce growth. Due to its anti-fibrotic and muscle-relaxing properties, we hypothesize that Botulinum Toxin A (BTX) can enhance traction-induced esophageal growth. METHODS: A retrospective two-center cohort study was conducted on children who underwent a BTX-enhanced Foker process for LGEA repair from 2021 to 2023. BTX (10 units/ml, 2 units/kg, per esophageal pouch) was applied at the time of traction initiation. Time on traction, complications, and anastomotic outcomes were compared against historical controls (Foker process without BTX) from 2014 to 2021. RESULTS: Twenty infants (LGEA type A:12, B:4, C:4; 35% reoperative; median [IQR] age 3 [2-5] months), underwent BTX-enhanced Foker process (thoracotomy with external traction: 9; minimally invasive [MIS] multi-staged internal traction: 11). Mean gap lengths were similar between BTX-enhanced external and external traction control patients (mean [SD], 50.6 mm [12.6] vs. 44.5 mm [11.9], p = 0.21). When compared to controls, the BTX-enhanced external traction process was significantly faster (mean [SD], 12.1 [1.6] days vs. 16.6 [13.2] without BTX, p = 0.04) despite similar preoperative gap lengths. There was no difference in time on traction for those undergoing a minimally invasive process. There were no significant differences in complications or anastomotic outcomes in either cohort. CONCLUSION: Botulinum toxin may play a role in accelerating the traction-induced esophageal growth process for LGEA repair. Minimizing time on traction can decrease sedation and paralysis burden while on external traction. Further studies are needed to elucidate the effects of BTX on the esophagus. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Retrospective, Two-center, Cohort study.
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Background: As part of a large science education effort, bacteriophages that lyse Mycobacterium smegmatis mc2155 continue to be discovered. Materials and Methods: Phages were isolated from soil samples from urban sites in the Northeastern United States. Their genomes were sequenced, assembled, and bioinformatically compared. Results: Three lytic siphoviruses belonging to subcluster B3 with high similarity to each other and other B3 mycobacteriophages were isolated. These phages contain double-stranded DNA genomes (68,754 to 69,495 bp) with high GC content (67.4-67.5%) and 102-104 putative protein coding genes. Notable features include a HicA-like toxin and 33 genes exclusive to subcluster B3. One phage had an intein in its terminase sequence. Conclusions: Genomic analyses of these phages provide insights into genome evolution and horizontal gene transfer (HGT). The networks for HGT are apparently vast and gene specific. Interestingly, a number of genes are found in both B3 and Gordonia DR phages.
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Background: The toxin-antitoxin (TA) system plays a vital role in the virulence and pathogenicity of Mycobacterium tuberculosis (M. tuberculosis). However, the regulatory mechanisms and the impact of gene mutations on M. tuberculosis transmission remain poorly understood. Objective: To investigate the influence of gene mutations in the toxin-antitoxin system on M. tuberculosis transmission dynamics. Method: We performed whole-genome sequencing on the analyzed strains of M. tuberculosis. The genes associated with the toxin-antitoxin system were obtained from the National Center for Biotechnology Information (NCBI) Gene database. Mutations correlating with enhanced transmission within the genes were identified by using random forest, gradient boosting decision tree, and generalized linear mixed models. Results: A total of 13,518 M. tuberculosis isolates were analyzed, with 42.29% (n = 5,717) found to be part of genomic clusters. Lineage 4 accounted for the majority of isolates (n = 6488, 48%), followed by lineage 2 (n = 5133, 37.97%). 23 single nucleotide polymorphisms (SNPs) showed a positive correlation with clustering, including vapB1 G34A, vapB24 A76C, vapB2 T171C, mazF2 C85T, mazE2 G104A, vapB31 T112C, relB T226A, vapB11 C54T, mazE5 T344C, vapB14 A29G, parE1 (C103T, C88T), and parD1 C134T. Six SNPs, including vapB6 A29C, vapB31 T112C, parD1 C134T, vapB37 G205C, Rv2653c A80C, and vapB22 C167T, were associated with transmission clades across different countries. Notably, our findings highlighted the positive association of vapB6 A29C, vapB31 T112C, parD1 C134T, vapB37 G205C, vapB19 C188T, and Rv2653c A80C with transmission clades across diverse regions. Furthermore, our analysis identified 32 SNPs that exhibited significant associations with clade size. Conclusion: Our study presents potential associations between mutations in genes related to the toxin-antitoxin system and the transmission dynamics of M. tuberculosis. However, it is important to acknowledge the presence of confounding factors and limitations in our study. Further research is required to establish causation and assess the functional significance of these mutations. These findings provide a foundation for future investigations and the formulation of strategies aimed at controlling TB transmission.
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Multiple compounds are related to the development of liver injury, such as toxins, drugs, and environmental pollutants. Although there are reports that the T-2 toxin can cause liver injury, its toxic mechanism remains unclear, which further impedes the development of effective antidotes. In this study, CRISPR-Cas9 genome-wide screening technology was used to identify transformation-related protein 53 inducible nuclear protein 1 (trp53inp1) as a toxic target of the T-2 toxin. Mechanism studies have shown that the T-2 toxin induced pyroptosis of macrophages (J774A.1 cells) by activating the trp53inp1/NF-κB/NLRP3/GSDMD-N pathway, leading to a subacute liver injury. Also, the new drug berberine (BER) identified through virtual screening significantly alleviated the subacute liver injury by competitively binding trp53inp1 via His224; the effect was better than those of the positive control drugs N-acetylcysteine (NAC) and disulfiram (DSF). In summary, the above results indicate that trp53inp1 is a key target for T-2 toxin to induce subacute liver injury and that inhibiting macrophage pyroptosis is a new method for treating liver injury. In addition, this study provides a new method and strategy for the discovery of key disease targets and the search for effective drugs.
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Shiga toxin (Stx) is the definitive virulence factor of Stx-producing Escherichia coli. This bacterial pathogen can contaminate food and threaten human health. Binding of the B subunit of Stx to the specific receptor globotriaosylceramide (Gb3) on the cell membrane is a key step for Stx to enter cells and exert its toxicity. In this work, we aimed to screen for aptamers targeting the Stx 2 B subunit, to interfere with the interaction of Stx2 B subunit and Gb3, thereby blocking Stx2 from entering cells. The results of molecular simulation docking, competitive ELISA, flow cytometry, and laser confocal microscopy confirmed that aptamers S4, S5, and S6 can mediate the interaction between Stx2 B subunit and Gb3. To further improve the inhibition effect, multiple aptamer sequences were tailored and were fused. The bivalent modification aptamer B2 inhibited Stx2 toxicity to Vero cells with inhibition rate of 53 %. Furthermore, the aptamer B2 reduced Stx2 damage to the mice, indicating that it has great potential to interfere with Stx2 binding to Gb3 receptors in vivo and in vitro. This work provides a theoretical and experimental basis for the application of aptamers in the inhibition of Stx2 toxicity and control of food hazards.
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OBJECTIVE: This systematic review aims to summarize and synthesize the evidence that investigates the secondary effects of the application of botulinum toxin (BT) into the masticatory muscles and its effects on bone density. MATERIALS AND METHODS: Database searches were conducted until March 19th, 2024. The quality of the studies was assessed by the Cochrane tool risk of bias for the randomized controlled trials and the ROBINS-I tool for non-randomized studies. The Cochrane Grading of Recommendations Assessment Development and Evaluation (GRADE) was used to evaluate the confidence in the overall evidence. RESULTS: Five studies looking at the effects of botulinum toxin on bone density and resorption when applied to masticatory muscles were found. No significant changes were observed in most of the studies when looking at the effects of botulinum toxin on mandibular condyle volume, density, mandibular angle thickness, and coronoid process volume. The only finding that was statistically and clinically relevant was the difference between patients who received a double application of BT when compared with patients who received a single application (SMD: -0.99 [95%CI: -1.94,-0.05]) on the volume of the mandibular angle. CONCLUSIONS: There is no clear pattern on whether the application of botulinum toxin is associated with bone resorption or not. Although some studies show statistical significance of the findings, the magnitude of the changes in bone density and their clinical significance are not completely clear. CLINICAL RELEVANCE: To understand the effectiveness of the use of botulinum toxin into the masticatory muscles and its possible secondary adverse effects on the density of the mandible.