Search

Japanese spotted fever is an emerging rickettsiosis caused by Rickettsia japonica and is characterized by high fever, rash, and eschar formation. Other symptoms are often vague and nonspecific and include headaches, nausea, vomiting, and myalgia. We present a case of a 46-year-old woman with Japanese spotted fever, complicated by transient bilateral sensorineural hearing loss and presenting cutaneous IgM/IgG immune complex vasculitis. The patient was admitted with a history of several days of high fever, generalized skin erythema, and hearing impairment. Laboratory findings revealed thrombocytopenia and elevated liver enzyme and C-reactive protein levels. Pure-tone audiometry revealed bilateral sensorineural hearing loss, and a skin biopsy revealed leukocytoclastic vasculitis with deposition of C3 and IgM on the vessel walls. Under the tentative diagnosis of rickettsiosis, scrub typhus, or Japanese spotted fever, the patient was treated with minocycline, and her symptoms improved within approximately 10 days. A definitive diagnosis was made on the basis of a serological test showing increased antibody levels against Rickettsia japonica. Japanese spotted fever can cause transient sensorineural hearing loss, a rare complication that presents with cutaneous IgM/IgG immune complex vasculitis., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Acute compartment syndrome(ACS) is a perilous consequence of trauma. Acute compartment syndrome's precise cause is yet unknown. We performed studies to confirm that acute compartment syndrome can be relieved by suppressing ferroptosis and activating the Nrf2/Hmox1 pathway., Methods: We generated an ACS rat model and we conducted next-generation sequencing(NGS) of skeletal muscle tissue and identified differentially expressed target genes. Ultimately, we performed in vivo experiments to validate the presence of ferroptosis and the Nrf2/Hmox1 pathway in ACS rats. After the minocycline intervention, the drug was evaluated for its effects on ACS by examining changes associated with ferroptosis., Results: The bioinformatics analysis identified that the genetic changes in the disease were mostly focused on ferroptosis, with noticeable modifications in Nrf2/Hmox1. Based on the in vivo results, it was observed that ACS rats exhibited significantly elevated levels of ferroptosis compared to the control rats. The suppression of the Nrf2/Hmox1 pathway mediated by minocycline improves outcomes in ACS and reduces tissue damage after intervention., Conclusion: Minocycline hinders ferroptosis via stimulating the Nrf2/Hmox1 pathway, which slows down the advancement of acute compartment syndrome., (© 2024. The Author(s).)

Background: Macrolide-resistant Mycoplasma pneumoniae (MRMP) strains are increasingly prevalent, leading to a rise in severe Mycoplasma pneumoniae pneumonia incidence annually, which poses a significant threat to children's health. This study aimed to compare the effectiveness and safety of oral minocycline and doxycycline for the treatment of severe MRMP pneumonia in children., Methods: This retrospective analysis included children treated for severe MRMP pneumonia at the Pediatric Department of Tongji Hospital, Shanghai, China, between September 2023 and January 2024 using minocycline and doxycycline. The patients were divided into four groups according to treatment: oral doxycycline alone (DOX group), oral minocycline alone (MIN group), oral doxycycline with intravenous glucocorticoids (DOXG group), and oral minocycline with intravenous glucocorticoids (MING group). Student's t-test, Mann-Whitney U test, and χ 2 or Fisher's exact tests were used for group comparisons., Results: A total of 165 patients were included in this study: 84 received minocycline, and 81 received doxycycline. The DOX group had higher fever resolution rates within 24, 48, and 72 h compared to the MIN group (63.2% vs. 31.8%, 79.0% vs. 63.6%, and 100% vs. 90.9%, respectively; all p < 0.05). The DOXG group showed higher fever resolution rates within 24 and 48 h than the MING group (92.3% vs. 83.4%, 100% vs. 92.7%, all p > 0.05). There were no statistically significant differences in time to imaging improvement, cough improvement, and disappearance of wet rales between groups, regardless of glucocorticoid combination. The longer the duration of fever prior to tetracycline therapy, the greater the likelihood of hypoxemia (p = 0.039) and a greater than two-fold elevation in the D-dimer level (p = 0.004).Univariate binary logistic regression model analysis revealed that CRP and erythrocyte sedimentation rate at disease onset were associated with defervescence within 24 h after treatment with tetracyclines alone (p = 0.020, p = 0.027), with erythrocyte sedimentation rate also influencing defervescence within 48 h (p = 0.022)., Conclusion: Doxycycline treatment resulted in a higher rate of defervescence than minocycline. Prompt treatment reduced the probability of pleural effusion, hypoxemia, pulmonary atelectasis, and D-dimer levels > 2 times the reference value., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

A 67-year-old woman was admitted to our hospital because of a complete right bundle branch block. She had been treated with minocycline for skin sarcoidosis and her symptoms had ameliorated four years previously. Gallium scintigraphy revealed an abnormal uptake in the heart but not in the skin or lungs. She was diagnosed with cardiac sarcoidosis, although an endomyocardial biopsy could not detect any sarcoid lesions. Immunohistochemical staining for Cutibacterium acnes was positive for granulomas of the skin lesions which had been previously biopsied. One year after starting the administration of steroids, her condition improved.

Haploinsufficiency of the transcriptional repressor ZBTB18/RP58 is associated with intellectual disability. However, the mechanisms causing this disability are unknown, and preventative measures and treatments are not available. Here, we assessed multiple behaviors in Zbtb18/Rp58 heterozygous-knockout mice, and examined local field potentials, DNA fragmentation, mitochondrial morphology, and performed histochemical and transcriptome analyses in the hippocampus to evaluate chronic inflammation. In wild-type mice, object location memory was present at a similar level at 2 and 4-5 months of age, and became impaired at 12-18 months. In contrast, Zbtb18/Rp58 heterozygous-knockout mice displayed early onset impairments in object location memory by 4-5 months of age. These mice also exhibited earlier accumulation of DNA and mitochondrial damage, and activated microglia in the dentate gyrus, which are associated with defective DNA repair. Notably, chronic minocycline therapy, which has neuroprotective and anti-inflammatory effects, attenuated age-related phenotypes, including accumulation of DNA damage, increased microglial activation, and impairment of object location memory. Our results suggest that Zbtb18/Rp58 activity is required for DNA repair and its reduction results in DNA and mitochondrial damage, increased activation of microglia, and inflammation, leading to accelerated declines in cognitive functions. Minocycline has potential as a therapeutic agent for the treatment of ZBTB18/RP58 haploinsufficiency-associated cognitive dysfunction., (© 2024. The Author(s).)

This study aimed to investigate the impact of minocycline on the alveolar bone in experimental periodontitis in rats. Thirty Wistar rats were randomly assigned to three groups: control without periodontitis; experimental periodontitis induced by ligature; experimental periodontitis + intraperitoneal administration minocycline for seven days. Ligatures remained in place in both periodontitis groups for 14 days. At the end of the experiment, the animals were euthanized and one hemimandible underwent micro-computed tomography (micro-CT) analysis to assess vertical bone loss and alveolar bone quality. Histopathological analysis was performed on the other hemimandible. Statistical analysis was performed using ANOVA with Tukey's post-test (p<0.05). The results showed a significant reduction in vertical bone loss in the animals treated with minocycline compared with untreated animals. Minocycline also preserved the alveolar bone thickness, number, spacing, and bone volume to tissue volume ratio. Histopathological analysis indicated that minocycline reduced bone resorption, decreased inflammatory response, and maintained the bone collagen fibers. This study demonstrated the effectiveness of minocycline in reducing vertical bone loss and preserved bone quality in rats with experimental periodontitis. The results of this study indicate that minocycline has the potential to serve as an additional treatment option for periodontitis. However, further research is warranted to assess the efficacy and safety of minocycline use in patients with periodontitis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Frazão et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The clinical outcome of intracranial infections caused by extensively drug-resistant Acinetobacter baumannii (XDRAB) remains unsatisfactory, even when treated with combined antibiotic therapy. This study successfully cured 1 patient with XDRAB intracranial infection after cranial surgery through a multichannel combination of drugs, providing a reference for the clinical treatment of severe XDRAB intracranial infection., Methods: The clinical data of a patient with an XDRAB intracranial infection after a craniocerebral operation were retrospectively analyzed, and the treatment approach for XDRAB intracranial infection was examined., Results: Upon the occurrence of XDRAB intracranial infection after craniocerebral surgery, the patient was given an intravenous injection of polymyxin B+ tigecycline + amikacin, while intrathecal injection of polymyxin B, and the intracranial infection was controlled and cured., Conclusions: Polymyxin B+ tigecycline + amikacin intravenous and intrathecal polymyxin B can benefit XDRAB intracranial infected patients after craniofacial surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Sepsis is associated with brain injury and acute brain inflammation, which can potentially transition into chronic inflammation, triggering a cascade of inflammatory responses that may lead to neurological disorders. Minocycline, recognized for its potent anti-inflammatory properties, was investigated in this study for its protective effects against sepsis-induced brain injury. Adult male C57 mice pretreated with minocycline (12.5, 25, and 50 mg/kg) 3 days before sepsis induction. An intraperitoneal injection of 5 mg/kg LPS was used to induce sepsis. Spontaneous locomotor activity (SLA) and weight changes were assessed over several days post-sepsis to monitor the recovery of the mice. The expression of inflammatory mediators and oxidative stress markers was assessed 24 h post sepsis. Septic mice exhibited significant weight loss and impaired SLA. Initially, minocycline did not attenuate the severity of weight loss (1 day) or SLA (4 h post-sepsis), but it significantly accelerated the recovery of the mice in later days. Minocycline dose-dependently mitigated sepsis-induced brain inflammation and oxidative stress. Our findings demonstrate that pretreatment with minocycline has the potential to prevent brain tissue damage and accelerate recovery from sepsis in mice, suggesting that minocycline may serve as a promising therapeutic intervention to protect against sepsis-induced neurological complications., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objectives: Carbapenem-resistant A. baumannii is a common cause of nosocomial meningitis, and it presents a challenge in terms of treatment because of limited therapeutic options. Intravenous tigecycline has been considered a potential salvage therapy against multi-drug-resistant Acinetobacter baumannii . However, its effectiveness is limited by its poor ability to cross the blood-brain barrier. As an alternative treatment option, intrathecal tigecycline has shown promise with its minimal side effects and high concentration in cerebrospinal fluid. Methods: In this report, we present a series of four cases infected with multi-drug-resistant A. baumannii following neurosurgery and treated with intrathecal tigecycline, including antimicrobial therapy. Results: The rate of successful microbiological response was 2 out of 3 cases (66%) in whom microbiological response could be tested anytime during the intrathecal therapy, whereas the 30-day survival rate after treatment completion was ¼ (25%). Conclusion: Although intrathecal tigecycline treatment has shown relative efficacy in achieving microbiological response, its impact on overall survival is still uncertain. Further studies involving larger groups of patients are necessary to evaluate the outcomes of intrathecal tigecycline therapy.

This study aims to investigate two key aspects in a mouse model of ocular hypertension (OHT): first, the time course of retinal ganglion cell (RGC) death and the parallel activation of caspase-3 (a-Casp3+ cells) to narrow the therapeutic window; and second, the effect of caspase-3 and microglia inhibition by minocycline on RGC rescue in this model. RGC loss after OHT induction was significant at day 7 and progressed to 30 days. However, anatomical RGC death was preceded by significant Casp3 activation on day 3. Microglial inhibition by minocycline did not alter the course of OHT or rescue RGCs but resulted in a decrease in a-Casp3+ cells and phagocytic and total microglia. Therefore, RGC death commitment occurs earlier than their loss of Brn3a expression, microglial cells do not exacerbate RGC loss, and while this death is primarily apoptotic, apoptosis inhibition does not rescue RGCs, suggesting that alternative death pathways play a role in glaucomatous injury.

Objective: Ischemic stroke is a leading cause of death and disability in individuals worldwide. Cerebral ischemia-reperfusion injury (CIRI) typically results in severe secondary injury and complications following reperfusion therapy. Microglia play critical roles in the inflammatory reaction of CIRI. However, less attention has been given to microglial death in this process. Our study aims to explore microglial death in CIRI and the effects and mechanism of minocycline treatment on microglia., Methods: A middle cerebral artery occlusion (MCAO) model was applied to induce CIRI in rats. At 0 h, 24 h and 48 h post-operation, rats were intraperitoneally injected with 45 mg/kg minocycline. Neurological deficit scoring, 2,3,5-triphenyltetrazolium chloride (TTC) staining, assessment of activated microglia and examination of mitochondrial structure were conducted and checked at 72 h after reperfusion. Additionally, an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R) model was established. BV-2 cells were treated with various pharmacological inhibitors of cell death or minocycline. Cell viability, lipid peroxidation, mitochondrial structure and function, and labile Fe 2+ and ferroptosis-associated gene/protein levels were measured. Hemin was used for further validation after transcriptome analysis., Results: In the MCAO and OGD/R models, ferroptosis was identified as a major form of microglial death. Minocycline inhibited microglia ferroptosis by reducing HO-1 expression. In addition, minocycline improved mitochondrial membrane potential, mitochondrial structures and microglial survival in vivo. Minocycline also decreased labile Fe 2+ levels, lipid peroxidation, and expression of ferritin heavy chain (FTH) and it improved mitochondrial structure and function in vitro. Upregulation of HO-1 counteracted the protective effect of minocycline., Conclusion: Ferroptosis is a major form of microglial death in CIRI. The protective mechanism of minocycline in CIRI partially hinges on its ability to effectively ameliorate microglia ferroptosis by downregulating HO-1 expression. Consequently, targeting microglia ferroptosis is a promising treatment for CIRI., (© 2024. The Author(s).)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Minocycline, a broad-spectrum tetracycline antibiotic, has been shown to possess anti-inflammatory and antioxidative effects in various neurodegenerative diseases. However, its specific effects on retinitis pigmentosa (RP) have not been thoroughly investigated. Therefore, the objective of this study was to explore the potential role of minocycline in treating RP. In this investigation, we used rd1 to explore the antioxidant effect of minocycline in RP. Minocycline therapy effectively restored retinal function and structure in rd1 mice at 14 days postnatal. Additionally, minocycline inhibited the activation of microglia. Moreover, RNA sequencing analysis revealed a significant downregulation in the expression of mitochondrial genes within the retina of rd1 mice. Further KEGG and GO pathway analysis indicated impaired oxidative phosphorylation and electron transport chain processes. TEM confirmed the presence of damaged mitochondria in photoreceptors, while JC-1 staining demonstrated a decrease in mitochondrial membrane potential, accompanied by an increase in mitochondrial reactive oxygen species (ROS) levels. However, treatment with minocycline successfully reversed the abnormal expression of mitochondrial genes and reduced the levels of mitochondrial ROS, thereby providing protection against photoreceptor degeneration. Collectively, minocycline demonstrated the ability to rescue photoreceptor cells in RP by effectively modulating mitochondrial homeostasis and subsequently inflammation. These findings hold significant implications for the development of potential therapeutic strategies for RP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The optimal dosage of minocycline remains unclear for Helicobacter pylori (H. pylori) eradication. We aimed to evaluate the efficacy and safety of four different regimens with minocycline and metronidazole compared to classical bismuth quadruple therapy for H. pylori rescue treatment., Materials and Methods: From March 2021 to March 2024, refractory H. pylori-infected patients with at least two previous treatment failures who received 14-day therapy with b.i.d. proton pump inhibitor 20 mg and bismuth 220 mg, plus tetracycline 400 mg q.i.d and metronidazole 400 mg q.i.d (BQT), or minocycline 50 mg q.i.d and metronidazole 400 mg q.i.d (PBMn 4 M 4 ), or minocycline 50 mg t.i.d and metronidazole 400 mg t.i.d (PBMn 3 M 3 ), or minocycline 50 mg b.i.d and metronidazole 400 mg q.i.d (PBMn 2 M 4 ), or minocycline 50 mg b.i.d and metronidazole 400 mg t.i.d (PBMn 2 M 3 ) were included in this retrospective study. H. pylori eradication was assessed by 13 C-urea breath test at least 6 weeks after treatment. All adverse effects during treatment were recorded., Results: Totally, 823 patients were enrolled: 251 with BQT, 97 with PBMn 4 M 4 , 191 with PBMn 3 M 3 , 108 with PBMn 2 M 4 , and 176 with PBMn 2 M 3 . The eradication rates of BQT, PBMn4M4, PBMn3M3, PBMn2M4, and PBMn2M3 were 89.2%, 87.6%, 91.6%, 88.0%, and 91.5%, respectively, by intention-to-treat analysis; 96.1%, 97.7%, 97.8%, 96.9%, and 97.6%, respectively, by modified intention-to-treat analysis; 97.1%, 97.5%, 97.7%, 96.8%, and 97.6%, respectively, by per-protocol analysis. Metronidazole resistance did not affect the efficacy of all groups. PBMn 2 M 3 group achieved the greatest compliance and the fewest moderate and severe adverse events., Conclusions: The novel bismuth-containing quadruple therapy with a low dose of minocycline and metronidazole is an alternative to classical bismuth quadruple therapy for H. pylori rescue treatment with superior safety and compliance., Trial Registration: ClinicalTrials.gov identifier: NCT06332599., (© 2024 John Wiley & Sons Ltd.)

Fragile X syndrome (FXS) is the primary hereditary cause of intellectual disability and autism spectrum disorder. It is characterized by exacerbated neuronal excitability, and its correction is considered an objective measure of treatment response in animal models, a marker albeit rarely used in clinical trials. Here, we used an extensive transcranial magnetic stimulation (TMS) battery to assess the neurophysiological effects of a therapy combining two disease-modifying drugs, lovastatin (40 mg) and minocycline (100 mg), administered alone for 8 weeks and in combination for 12 weeks, in 19 patients (mean age of 23.58 ± 1.51) with FXS taking part in the LOVAmix trial. The TMS battery, which included the resting motor threshold, short-interval intracortical inhibition, long-interval intracortical inhibition, corticospinal silent period, and intracortical facilitation, was completed at baseline after 8 weeks of monotherapy (visit 2 of the clinical trial) and after 12 weeks of dual therapy (visit 4 of the clinical trial). Repeated measure ANOVAs were performed between baseline and visit 2 (monotherapy) and visit 3 (dual therapy) with interactions for which monotherapy the participants received when they began the clinical trial. Results showed that dual therapy was associated with reduced cortical excitability after 20 weeks. This was reflected by a significant increase in the resting-motor threshold after dual therapy compared to baseline. There was a tendency for enhanced short-intracortical inhibition, a marker of GABAa-mediated inhibition after 8 weeks of monotherapy compared to baseline. Together, these results suggest that a combined therapy of minocycline and lovastatin might act on the core neurophysiopathology of FXS. This trial was registered at clinicaltrials.gov (NCT02680379)., (© 2024 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Competing Interests: The authors have no conflicts of interest to declare.

Although many treatments are available for acne, these can be limited by lack of effectiveness, patient tolerance and adherence, and accessibility. This review provides a comprehensive summary of the latest developments in acne management, exploring a range of topical, systemic, and procedural treatments. The mechanisms of action, pivotal trial data, and potential role in clinical practice are reviewed for emerging therapies such as 1726 nm laser, sarecycline, clascoterone, trifarotene, minocycline foam, and fixed-dose combination topicals. The clinical pipeline is also summarized. In addition, opportunities to improve the patient experience with spironolactone and isotretinoin are discussed., Competing Interests: Disclosure Dr J.S. Barbieri has received consulting fees from Dexcel pharma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Nocardiosis in patients after allogeneic hematopoietic stem cell transplantation (HSCT) is rare, but is associated with a significant mortality risk. Although trimethoprim-sulfamethoxazole (TMP/SMX) remains the cornerstone of nocardiosis treatment, optimal alternative therapies for patients intolerant to TMP/SMX are not well-established. Herein, we report a case of disseminated nocardiosis with bacteremia and multiple lesions in the lungs and brain caused by Nocardia farcinica, in a 60-year-old man who had previously undergone allogeneic HSCT and was receiving immunosuppressants for severe chronic graft-versus-host disease. The patient received atovaquone for the prophylaxis of Pneumocystis pneumonia because of a previous serious allergic reaction to TMP/SMX. The patient was initially treated with imipenem/cilastatin and amikacin, which were later switched to ceftriaxone and amikacin based on the results of antimicrobial susceptibility testing. After switching to oral levofloxacin and a standard dose of minocycline, the patient experienced a single recurrence of brain abscesses. However, after switching to oral moxifloxacin and high-dose minocycline, the patient did not experience any relapses during the subsequent two years and seven months of treatment. In treating nocardiosis with brain abscesses, it is crucial to select oral antibiotics based on the antimicrobial susceptibility test results and pharmacokinetics, especially when TMP/SMX is contraindicated. A combination of oral moxifloxacin and high-dose minocycline could be a promising alternative therapy., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Purpose: Minocycline suppresses chemotherapy-induced neuroinflammation in preclinical models, but its effects in cancer survivors are unknown. This study evaluated the longitudinal effects of minocycline on affective behaviors, cognitive functions, and inflammation in women with breast cancer (BC) undergoing chemotherapy., Methods: This is a pilot, double-blind, randomized controlled trial of oral minocycline (100 mg BID) versus placebo for chemotherapy-induced affective disorders in women initiating chemotherapy for stage I-III BC. Participants received minocycline or placebo up to one week before chemotherapy, continuing through cycle 4 (C4). Epidemiologic Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI) were assessed at baseline, each cycle of chemotherapy (C1-C4), 2-3-week post-chemotherapy (end of chemotherapy), and 6-month post-chemotherapy (6 M) as the primary outcomes. Sub-group analysis of CES-D and STAI based on the severity of symptoms was also performed. Changes in self-reported cognition and serum inflammatory markers were also evaluated., Results: Fifty-seven women enrolled and 55 completed the study. Except for Interleukin-8 (p ≤ 0.03), changes in inflammatory markers, cognitive function, CES-D, and STAI were not significantly different between groups from baseline to any cycle or post-chemotherapy time point (all p > 0.05), adjusting for baseline scores. Increases in serum Interleukin-8 from baseline to C4 and 6 M were ameliorated by minocycline (p < 0.05). The sub-group symptomatic for depression (CES-D > = 16 at baseline) treated with minocycline had a greater reduction in CES-D score compared to placebo from baseline to 6 M (p = 0.01)., Conclusion: Despite attenuation of IL-8, minocycline did not alter self-reported affective symptoms or cognition in this cohort of BC survivors undergoing chemotherapy. The effect of minocycline on BC survivors symptomatic for depression before chemotherapy warrants further investigation., (© 2024. The Author(s).)

A 72 year-old male patient with a history of a hepatic cyst presented to our hospital with epigastric pain. The cyst had enlarged to approximately 130 mm and was diagnosed as a symptomatic hepatic cyst. Percutaneous cyst drainage was deemed challenging because of the risk of intestinal perforation; therefore, transgastric endoscopic ultrasound-guided hepatic cyst drainage was performed with external nasal cyst drainage. After cyst shrinkage was confirmed, minocycline hydrochloride was injected into the cyst through the nasal drainage tube, and the nasal cyst drainage was removed. Nine months after treatment, the cyst diameter markedly reduced to 12 mm on computed tomography, and the symptoms improved. In cases where surgery is complex or it is difficult to secure a percutaneous puncture line, endoscopic ultrasound-guided drainage and minocycline hydrochloride injection may be effective if a puncture route can be secured under endoscopic ultrasound., (© 2024. Japanese Society of Gastroenterology.)

Human granulocytic anaplasmosis (HGA) is a tick-borne infection caused by Anaplasma phagocytophilum. Only seven cases of HGA have been reported in Japan to date. We report the case of a 61-year-old female farmer who developed HGA with rash and rhabdomyolysis. The patient had fever and erythema covering the entire body, including the palms. An induration with an eschar was observed on the right leg, indicating that the patient had been bitten by a tick. Elevated serum creatinine and creatinine kinase levels and hematuria indicated rhabdomyolysis. We suspected Japanese spotted fever, a tick-borne illness caused by Rickettsia Japonica, and administered minocycline and ciprofloxacin for a week. Transient neutropenia and thrombocytopenia were observed, but the symptoms improved. Polymerase chain reaction (PCR) and antibody tests for R. japonica and Orientia tsutsugamushi, which causes scrub typhus, were both negative. The PCR test for severe fever with thrombocytopenia syndrome virus was also negative. Antibodies against A. phagocytophilum-related proteins were detected by western blotting, indicating seroconversion of IgG with paired serum samples, and the patient was diagnosed with HGA. HGA should be suspected in acute febrile patients with a history of outdoor activity and cytopenia, with or without a rash. A testing system and the accumulation of cases in Japan are necessary for the early diagnosis and appropriate treatment of HGA., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Introduction: Tigecycline has a broad spectrum of activity, including activity against drug-resistant Gram-positive and -negative microorganisms. Its side effects are significant, but hypoglycemia is a rare finding during treatment. We aim to present an event of severe hypoglycemia in a patient with type 2 diabetes mellitus with replacement renal therapy, and hemodialysis after initiating tigecycline., Case Presentation: A 54-year-old female diagnosed with type 2 diabetes mellitus was under treatment with basal-bolus insulin therapy and oral antihypertensive drugs. She started hemodialysis 24 months ago. She complained of recurrent fever for the last seven months and was treated with several antibiotics. In two separate blood cultures, she tested positive for methicillin-resistant Staphylococcus epidermidis (MRSE). Based on the antibiogram, we started treatment with tigecycline 100 mg/day. After 6-8 hours from the first dose, the patient is complicated with events of hypoglycemia and then continues with severe hypoglycemia (40-47 mg/dL). The patient continued to have hypoglycemia for about 16-18 hours after the last dose. We didn't find any reasons to explain the cause of episodes of hypoglycemia. She did not have high blood insulin levels (insulin 4.11 mIU/L [range 2.6-24.9]). We followed her for six months and the patient did not experience episodes of hypoglycemia., Conclusions: The association of severe hypoglycemia with tigecycline treatment is a very rare event and published papers on this topic are limited. Clinicians should be aware of this rare event when administering tigecycline and should routinely check blood glucose level during the treatment., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Entela Puca, Edmond Puca, Klei Vrekaj, Dea Puca.)

Periodontitis, an inflammatory bone resorption disease associated with dental plaque, poses significant challenges for effective treatment. In this study, we developed Mino@ZIF-8 nanoparticles inspired by the periodontal microenvironment and the unique properties of zeolitic imidazolate framework 8, aiming to address the complex pathogenesis of periodontitis. Transcriptome analysis revealed the active engagement of Mino@ZIF-8 nanoparticles in innate and adaptive inflammatory host defense and cellular metabolic remodeling. Through sustained release of the anti-inflammatory and antibacterial agent minocycline hydrochloride (Mino) and the generation of Zn 2+ with pro-antioxidant effects during degradation, Mino@ZIF-8 nanoparticles synergistically alleviate inflammation and oxidative damage. Notably, our study focuses on the pivotal role of zinc ions in mitochondrial oxidation protection. Under lipopolysaccharide (LPS) stimulation, periodontal ligament cells undergo a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis, leading to reduced ATP production and increased reactive oxygen species levels. However, Zn 2+ effectively rebalances the glycolysis-OXPHOS imbalance, restoring cellular bioenergetics, mitigating oxidative damage, rescuing impaired mitochondria, and suppressing inflammatory cytokine production through modulation of the AKT/GSK3β/NRF2 pathway. This research not only presents a promising approach for periodontitis treatment but also offers novel therapeutic opportunities for zinc-containing materials, providing valuable insights into the design of biomaterials targeting cellular energy metabolism regulation.

Background: Stenotrophomonas maltophilia is an opportunistic, gram-negative bacillus with few therapeutic options due to a high level of intrinsic resistance. Trimethoprim/sulfamethoxazole (SXT) is recommended as the first-line treatment; however, minocycline (MIN) has been shown to have similar clinical outcomes in treating S. maltophilia and addresses concern for increasing resistance to SXT., Objective: The objective of this study is to evaluate the efficacy and safety outcomes of nonurinary, monomicrobial infections due to S. maltophilia in hospitalized patients treated with MIN or SXT., Methods: This was a retrospective study of hospitalized adult patients receiving MIN or SXT for nonurinary monomicrobial S. maltophilia infection from April 1, 2018 to March 31, 2020. The primary outcome was clinical disposition classified as rates of clinical failure, clinical improvement, or clinical success., Results: Eighty-two patients (88.2%) received MIN and 11 patients (11.8%) received SXT initially. Clinical failure occurred in 16 (19.5%) patients in the MIN group and in 4 (36.4%) patients in the SXT group ( P = 0.242). Clinical improvement occurred in 11 (13.4%) patients in the MIN group and in 1 (9.1%) patient in the SXT group ( P = 1.0). Clinical success occurred in 55 (67.1%) patients in the MIN group and in 6 (54.5%) patients in the SXT group ( P = 0.503). Total duration of antimicrobial therapy ( P = 0.3198), in-hospital mortality ( P = 1.0), hospital length of stay ( P = 0.9668), intensive care unit (ICU) length of stay ( P = 0.1384), and 30-day readmission ( P = 0.686) were similar between groups., Conclusions and Relevance: Rates of clinical failure, clinical improvement, or clinical success were similar between MIN and SXT for nonurinary monomicrobial S. maltophilia infections., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.L.C. has served on advisory boards for Melinta, Ferring, LaJolla, Entasis, and MicroGenDX. A.L.C. serves as the site principal investigator for a retrospective chart studies sponsored by Shionogi and Karius. She does not receive salary support or funding for involvement with these studies.

Background: To evaluate the effects of antimicrobial peptides (AMPs) on Stage III Grade B periodontitis., Methods: This trial abided by the principle of consistency test, approved by ethics committee and registered in clinical trials. All qualified 51 patients with Stage III Grade B periodontitis were randomly divided into three groups: SRP group, SRP with minocycline hydrochloride (Mino group) as Control groups, and SRP with AMPs (AMP group) as the Test group. Clinical examinations and subgingival plaques were monitored at baseline and at 7 and 90 days after treatment in the SRP, SRP with AMP and Mino groups., Results: The AMP group (Test group) had a reduced PD (Periodontal probing depth) and an attachment gain significantly higher than SRP and Mino groups (Control groups) at day 90. The abundance of periodontal pathogens was decreased in the AMP group at 7 and 90 days compared with the SRP group and Mino group. Only the AMP group showed an increase the abundance of periodontal probiotics including Capnocytophaga, Gemella, and Lactobacillus at 7 and 90 days., Conclusions: This study shows that AMPs as an adjunct to SRP promote additional clinical and microbiological benefits in the treatment of Stage III Grade B periodontitis., (© 2023 Wiley Periodicals LLC.)

Background: Tigecycline, a glycylcycline antibiotic is a promising option for the treatment of single or multidrug resistant pathogens. The aim of the study was to evaluate the in-vitro Tigecycline susceptibility of various pathogens from clinical samples received at the tertiary care hospitals in South India., Methods: The analysis of specimens from patients admitted were carried out in this prospective cross sectional study. The identification and antimicrobial susceptibility testing was performed by semi-automated Vitek 2 systems and Kirby Bauer method. Pattern of data analysis was done by descriptive statistics., Results: Among 2574 isolates, 812 isolates were Gram positive pathogens and 1762 isolates were Gram negative pathogens. Resistance to Tigecycline was more common among Gram negative pathogens (18.62%) in comparison to the Gram positive pathogens (0.49%). Among 740 Extended Spectrum Beta Lactamases (ESBL) producers such as Klebsiella species & E coli , 629 isolates were susceptible, and 93 isolates were resistant to the tigecycline. All the methicillin resistant Staphylococcus aureus (MRSA) isolates were susceptible to tigecycline., Conclusion: Multidrug resistant (MDR) pathogens like Acinetobacter species, and Klebsiella species were found to be highly effective in vitro to tigecycline for elimination of infections caused by both Gram positive and Gram negative pathogens. The use of combination therapy becomes crucial to prevent the development of Pan Drug resistance., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Remash A et al.)

The prognosis for patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) remains dismal. It is generally accepted that combination cancer therapies offer the most promise, such as Folforinox, despite their associated high toxicity. This study addresses the issue of chemoresistance by introducing a complementary dual priming approach to attenuate the DNA repair mechanism and to improve the efficacy of a type 1 topoisomerase (Top1) inhibitor. The result is a regimen that integrates drug-repurposing and nanotechnology using 3 clinically relevant FDA-approved agents (1) Top1 inhibitor (irinotecan) at subcytotoxic doses (2) benzoporphyrin derivative (BPD) as a photoactive molecule for photodynamic priming (PDP) to improve the delivery of irinotecan within the cancer cell and (3) minocycline priming (MNP) to modulate DNA repair enzyme Tdp1 (tyrosyl-DNA phosphodiesterase) activity. We demonstrate in heterotypic 3D cancer models that incorporate cancer cells and pancreatic cancer-associated fibroblasts that simultaneous targeting of Tdp1 and Top1 were significantly more effective by employing MNP and photoactivatable multi-inhibitor liposomes encapsulating BPD and irinotecan compared to monotherapies or a cocktail of dual or triple-agents. These data are encouraging and warrant further work in appropriate animal models to evolve improved therapeutic regimens., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier B.V.)

Aim: 3Mixtatin (a combination of Metronidazole, Minocycline, and Ciprofloxacin along with statins) is a novel biomaterial in pulp therapy, while Mineral Trioxide Aggregate (MTA) is considered the gold standard in endodontics. This study aimed to compare the clinical and radiographic success rates of MTA and 3Mixtatin in pulp therapy of primary teeth., Methods and Materials: MEDLINE (PubMed), CENTRAL, Web of Science, Scopus, ProQuest databases, and Google Scholar were searched to identify randomized controlled trials (RCTs) on pulp therapy with 3Mixtatin and MTA in primary teeth, published up to February 2023. It should be noted that the protocol was previously registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021243626). RCTs were assessed independently by two researchers in terms of eligibility and quality. Data extracted and tabulated. The Cochrane Risk of Bias (RoB-2) tool was used to assess the risk of bias. The effect sizes were evaluated utilizing risk ratios (RRs). The heterogeneity investigation was conducted utilizing I² measurement at α = 0.10., Results: Out of 86 retrieval records, four articles met the inclusion criteria. Based on clinical and radiographic outcomes, the application of 3Mixtatin in the pulp therapy of primary teeth was as successful as MTA in 12 months (Clinical RR = 1.087 | Radiographic RR = 2.132). The RoB-2 tool showed a low risk of bias in all included RCTs., Conclusion: The limited evidence showed the clinical and radiographic efficacy of 3Mixtatin as a potential alternative to MTA. Further empirical research with larger sample sizes and strict methodology will be essential to substantiate this assertion., (© 2024. The Author(s), under exclusive licence to British Dental Association.)

Background: Difficulty in obtaining tetracycline, increased adverse reactions, and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple therapy. Therefore, the search for new alternative drugs has become one of the research hotspots. In recent years, minocycline, as a semisynthetic tetracycline, has demonstrated good potential for eradicating Helicobacter pylori ( H. pylori ) infection, but the systematic evaluation of its role remains lacking., Aim: To explore the efficacy, safety, and compliance of minocycline in eradicating H. pylori infection., Methods: We comprehensively retrieved the electronic databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang database as of October 30, 2023, and finally included 22 research reports on H. pylori eradication with minocycline-containing regimens as per the inclusion and exclusion criteria. The eradication rates of H. pylori were calculated using a fixed or a random effect model, and the heterogeneity and publication bias of the studies were measured., Results: The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall H. pylori eradication rates, reaching 82.3% [95% confidence interval (CI): 79.7%-85.1%] in the intention-to-treat analysis and 90.0% (95%CI: 87.7%-92.4%) in the per-protocol analysis. The overall safety and compliance of the minocycline-containing regimens were good, demonstrating an overall incidence of adverse reactions of 36.5% (95%CI: 31.5%-42.2%). Further by traditional meta-analysis, the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse effects. Most of the adverse reactions were mild to moderate and well-tolerated, and dizziness was relatively prominent in the minocycline-containing regimens (16%)., Conclusion: The minocycline-containing regimens demonstrated good efficacy, safety, and compliance in H. pylori eradication. Minocycline has good potential to replace tetracycline for eradicating H. pylori infection., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Minocycline is an FDA-approved secondary-generation tetracycline antibiotic. It is a synthetic antibiotic having many biological effects, such as antioxidant, anti-inflammatory, anti-cancer, and neuroprotective functions. This study discusses the pharmacological mechanisms of preventive and therapeutic effects of minocycline. Specifically, it provides a comprehensive overview of the molecular pathways by which minocycline acts on the different cancers, including ovarian, breast, glioma, colorectal, liver, pancreatic, lung, prostate, melanoma, head and neck, leukemia, and non-cancer diseases such as Alzheimer's disease, Parkinson, schizophrenia, multiple sclerosis, Huntington, polycystic ovary syndrome, and coronavirus disease 19. Minocycline may be a potential medication for these disorders due to its strong blood-brain barrier penetrance. It is also widely accepted as a specific medication, has a well-known side-effect characteristic, is reasonably priced, making it appropriate for continuous use in managing diseases, and has been demonstrated as an oral approach because it is effectively absorbed and accomplished almost all of the body's parts., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Delirium is a potentially severe form of acute encephalopathy. Minocycline has neuroprotective effects in animal models of neurologic diseases; however, data from human studies remain scarce., Research Question: Does the neuroprotective effect of minocycline prevent delirium occurrence in critically ill patients?, Study Design and Methods: This study was a randomized, placebo-controlled, double-anonymized trial conducted in four ICUs. Patients aged 18 years or older were eligible and randomized to receive minocycline (100 mg, twice daily) or placebo. The primary outcome was delirium incidence within 28 days or before ICU discharge. Secondary outcomes included days in delirium during ICU stay, delirium/coma-free days, length of mechanical ventilation, ICU length of stay, ICU mortality, and hospital mortality. The kinetics of various inflammatory (IL-1β, IL-6, IL-10, and C-reactive protein) and brain-related biomarkers (brain-derived neurotrophic factor and S100B) were used as exploratory outcomes., Results: A total of 160 patients were randomized, but one patient in the placebo group died before treatment; thus the data from 159 patients were analyzed (minocycline, n = 84; placebo, n = 75). After the COVID-19 pandemic it was decided to stop patient inclusion early. There was a small but significant decrease in delirium incidence: 17 patients (20%) in the minocycline arm compared with 26 patients (35%) in the placebo arm (P = .043). No other delirium-related outcomes were modified by minocycline treatment. Unexpectedly, there was a significant decrease in hospital mortality (39% vs. 23%; P = .029). Among all analyzed biomarkers, only plasma levels of C-reactive protein decreased significantly after minocycline treatment (F = 0.75, P = .78, within time; F = 4.09, P = .045, group × time)., Interpretation: Our findings in this rather small study signal a possible positive effect of minocycline on delirium incidence. Further studies are needed to confirm the benefits of this drug as a preventive measure in critically ill patients., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT04219735; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older., Objective: The objective of this study was to provide evidence-based recommendations for the management of acne., Methods: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations., Results: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements., Limitations: Analysis is based on the best available evidence at the time of the systematic review., Conclusions: These guidelines provide evidence-based recommendations for the management of acne vulgaris., Competing Interests: Conflicts of interest Rachel V.S. Reynolds, MD, Carol E. Cheng, MD, Kelly Druby, Megha M. Tollefson, MD, and Jung Min Han, PharmD, MS, have no relationships to disclose. Howa Yeung, MD, MS, serves as an investigator for American Acne & Rosacea Society, Department of Veterans Affairs, and National Institutes of Health receiving grants and research funding; as an independent contractor for American Academy of Dermatology and Journal of the American Medical Association receiving fees; as a speaker/faculty educator for Dermatology Digest receiving honoraria. Fran Cook-Bolden, MD, serves as an advisory board member for AbbVie, Dermavant Sciences, Inc., Galderma Global, Novartis, Ortho Dermatologics, and Pfizer Inc. receiving honoraria; as an investigator for Arcutis Biotherapeutics receiving grant and research funding; as a speaker for Galderma Laboratories, LP, Journey Medical Corporation, and Ortho Dermatologics receiving honoraria; as others for Topix Pharmaceuticals, Inc. receiving other financial benefit. Seemal R. Desai, MD, serves an advisory board member for Foundation for Research & Education of Dermatology receiving fees; as a consultant for AbbVie, Allergan, Inc, Almirall, Amgen, Apogee, Avita, Ballature Beauty, Beiersdorf, Inc., Bristol-Myers Squibb, Candela Corporation, Cassiopea S.p.A., Castle Biosciences, Cutera, Inc., Dermavant Sciences, Dermira, Eli Lilly and Company, EPI Health, Ferndale Laboratories, Inc., Foamix, Galderma Laboratories, LP, Gore Range Capital, Hyphens Pharma, Incyte Corporation, Janssen Pharmaceuticals, Inc, Johnson and Johnson, Leo Pharma Inc., L'Oreal USA Inc., Lyceum Health, Ortho Dermatologics, Pfizer Inc., Revision Skincare, Sanofi/Regeneron, Scientis, Skin Science Advisors, UCB, Verrica Pharmaceuticals Inc., and VYNE Therapeutics receiving fees, honoraria, and/or stock options; as an investigator for AOBiome, LLC, Atacama Therapeutics, Dermavant Sciences, Incyte Corporation, and SkinMedica, Inc. receiving grants and research funding; as a speaker for AbbVie, Dermira, Galderma Laboratories, LP., and Pfizer Inc. receiving fees; as a stockholder for Gore Range Capital; as other role for Medscape receiving fees. Esther E. Freeman, MD, PhD, serves as an investigator for International League of Dermatologic Societies and National Institutes of Health receiving grants and research funding; as an author for UptoDate, Inc. and British Journal of Dermatology, receiving honoraria or salary; as a speaker for Harvard University. Jonette E. Keri, MD, PhD, serves as an advisory board member for Ortho Dermatologics receiving honoraria; as a consultant for Almirall receiving fees; as an investigator for Galderma USA receiving grants and research funding; as a speaker for Foamix Pharmaceuticals Ltd and VYNE Therapeutics receiving honoraria. Linda F. Stein Gold, MD, serves as an advisory board member for AbbVie, Almirall, Aqua, Dermavant Sciences, Foamix, Galderma Laboratories, L.P., GlaxoSmithKline, Incyte Corporation, La Roche-Posay Laboratorie Pharmaceutique, LEO Pharma, US, Lilly ICOS LLC, Merz Pharmaceuticals, LLC, Pfizer Inc., Promius Pharmaceuticals, Sanofi/Regeneron, Taro Pharm, and Valeant Pharmaceuticals International receiving honoraria; as a consultant for AnaptysBio, BMS, Botanix Pharmaceuticals, Cutera, Inc., Incyte Corporation, Janssen Scientific Affairs, LLC, Sol-Gel Technologies, Taro Pharm, The Acne Store, and UCB receiving honoraria or grants and research funding; as an investigator for AbbVie, Allergan, Inc., AnaptysBio, Galderma Laboratories, L.P., Leo Pharma Inc., Novartis Pharmaceuticals Corp., Pfizer Inc., Topica, and Valeant Pharmaceuticals International receiving grants and research funding; as a speaker for Actavis, Almirall, BMS, Dermira, Pfizer Inc., Sanofi/Regeneron, Sun Pharmaceutical Industries Ltd., and VYNE Therapeutics receiving honoraria. Jerry K. L. Tan, MD, serves as an advisory board member for Abbott Laboratories, Cutera, Inc., Galderma Laboratories, L.P, and Sun Pharmaceutical Industries Ltd receiving honoraria or grants and research funding; as a consultant for Bausch Health, Boots, Galderma Research & Development, LLC, and Loreal Research and Innovation receiving honoraria; as an independent contractor for Norvatis receiving fees; as an investigator for Allergan, AnaptysBio, Cutera, Inc., Eli Lilly and Co., Galderma Laboratories, L.P, Lilly ICOS LLC, Pfizer, and UCB for receiving grants and research funding; as a speaker for Bausch Health, LEO Laboratories Ltd (LEO Pharma), and Vichy Laboratories receiving honoraria. Jonathan S. Weiss, MD, serves as an advisory board member for Bristol-Myers Squibb, Dermavant Sciences, Foamix, Galderma Laboratories, L.P., Incyte Corporation, Novartis, and UCB receiving honoraria; as a consultant for Arcutis, Inc., Biofrontera, Cutera, Inc., Leo Pharma Inc, Ortho Dermatologics, and UCB receiving fees or honoraria; as an investigator for AbbVie, Bausch Health, Biofrontera, Bristol-Myers Squibb, Cutera, Inc., Dermavant Sciences, Foamix, Galderma Laboratories, L.P., LEO Pharma, Mindera, Moberg Pharma North, America LLC, Novartis, Palvella Therapeutics, and Verrica Pharmaceuticals Inc receiving grants and research funding; as a speaker for AbbVie, Arcutis, Inc., Galderma Laboratories, L.P., Ortho Dermatologics, Regeneron, and Sanofi Genzyme receiving honoraria. Peggy A. Wu, MD, serves as others for UptoDate, Inc. receiving honoraria. Andrea L. Zaenglein, MD, serves as a consultant for Church & Dwight Co., Inc. and UCB receiving fees or honoraria; as an investigator for AbbVie, Arcutis Biotherapeutics, Biofrontera AG, Galderma Laboratories, L.P., and Incyte Corporation receiving grants and research funding. John S. Barbieri, MD, MBA serves as investigator for National Institutes of Health and National Psoriasis Foundation receiving grants and research funding., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Abstract: The Center for Disease Control and Prevention estimates that 75% of reported cases of traumatic brain injury (TBI) are mild, where chronic pain and depression are 2 of the most common symptoms. In this study, we used a murine model of repeated mild TBI to characterize the associated pain hypersensitivity and affective-like behavior and to what extent microglial reactivity contributes to these behavioral phenotypes. Male and female C57BL/6J mice underwent sham or repeated mild traumatic brain injury (rmTBI) and were tested for up to 9 weeks postinjury, where an anti-inflammatory/neuroprotective drug (minocycline) was introduced at 5 weeks postinjury in the drinking water. Repeated mild traumatic brain injury mice developed cold nociceptive hypersensitivity and negative affective states, as well as increased locomotor activity and risk-taking behavior. Minocycline reversed negative affect and pain hypersensitivities in male but not female mice. Repeated mild traumatic brain injury also produced an increase in microglial and brain-derived neurotropic factor mRNA transcripts in limbic structures known to be involved in nociception and affect, but many of these changes were sex dependent. Finally, we show that the antiepileptic drug, gabapentin, produced negative reinforcement in male rmTBI mice that was prevented by minocycline treatment, whereas rmTBI female mice showed a place aversion to gabapentin. Collectively, pain hypersensitivity, increased tonic-aversive pain components, and negative affective states were evident in both male and female rmTBI mice, but suppression of microglial reactivity was only sufficient to reverse behavioral changes in male mice. Neuroinflammation in limbic structures seems to be a contributing factor in behavioral changes resulting from rmTBI., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Background: The presence of plasmid-mediated resistance-nodulation-division (RND) efflux pump gene cluster tmexCD1-toprJ1 and its related variants has been associated with heightened resistance to tigecycline, thus diminishing its effectiveness. In this study, we explored the potential of gramine, a naturally occurring indole alkaloid, as an innovative adjuvant to enhance the treatment of infections caused by K. pneumoniae carrying tmexCD-toprJ-like gene clusters., Methods: The synergistic potential of gramine in combination with antibiotics against both planktonic and drug-tolerant multidrug-resistant Enterobacterales was evaluated using the checkerboard microbroth dilution technique and time-killing curve analyses. Afterwards, the proton motive force (PMF) of cell membrane, the function of efflux pump and the activity of antioxidant system were determined by fluorescence assay and RT-PCR. The intracellular accumulation of tigecycline was evaluated by HPLC-MS/MS. The respiration rate, bacterial ATP level and the NAD + /NADH ratio were investigated to reveal the metabolism state. Finally, the safety of gramine was assessed through hemolytic activity and cytotoxicity assays. Two animal infection models were used to evaluate the in vivo synergistic effect., Results: Gramine significantly potentiated tigecycline and ciprofloxacin activity against tmexCD1-toprJ1 and its variants-positive pathogens. Importantly, the synergistic activity was also observed against bacteria in special physiological states such as biofilms and persister cells. The mechanism study showed that gramine possesses the capability to augment tigecycline accumulation within cells by disrupting the proton motive force (PMF) and inhibiting the efflux pump functionality. In addition, the bacterial respiration rate, intracellular ATP level and tricarboxylic acid cycle (TCA) were promoted under the treatment of gramine. Notably, gramine effectively restored tigecycline activity in multiple animal infection models infected by tmexCD1-toprJ1 positive K. pneumoniae (RGF105-1)., Conclusion: This study provides the first evidence of gramine's therapeutic potential as a novel tigecycline adjuvant for treating infections caused by K. pneumoniae carrying tmexCD-toprJ-like gene clusters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Importance: Existing therapies to slow geographic atrophy (GA) enlargement in age-related macular degeneration (AMD) have relatively modest anatomic efficacy, require intravitreal administration, and increase the risk of neovascular AMD. Additional therapeutic approaches are desirable., Objective: To evaluate the safety and possible anatomic efficacy of oral minocycline, a microglial inhibitor, for the treatment of GA in AMD., Design, Setting, and Participants: This was a phase 2, prospective, single-arm, 45-month, nonrandomized controlled trial conducted from December 2016 to April 2023. Patients with GA from AMD in 1 or both eyes were recruited from the National Institutes of Health (Bethesda, Maryland) and Bristol Eye Hospital (Bristol, UK). Study data were analyzed from September 2022 to May 2023., Intervention: After a 9-month run-in phase, participants began oral minocycline, 100 mg, twice daily for 3 years., Main Outcomes and Measures: The primary outcome measure was the difference in rate of change of square root GA area on fundus autofluorescence between the 24-month treatment phase and 9-month run-in phase., Results: Of the 37 participants enrolled (mean [SD] age, 74.3 [7.6] years; 21 female [57%]), 36 initiated the treatment phase. Of these participants, 21 (58%) completed at least 33 months, whereas 15 discontinued treatment (8 by request, 6 for adverse events/illness, and 1 death). Mean (SE) square root GA enlargement rate in study eyes was 0.31 (0.03) mm per year during the run-in phase and 0.28 (0.02) mm per year during the treatment phase. The primary outcome measure of mean (SE) difference in enlargement rates between the 2 phases was -0.03 (0.03) mm per year (P = .39). Similarly, secondary outcome measures of GA enlargement rate showed no differences between the 2 phases. The secondary outcome measures of mean difference in rate of change between 2 phases were 0.2 letter score per month (95% CI, -0.4 to 0.9; P = .44) for visual acuity and 0.7 μm per month (-0.4 to 1.8; P = .20) for subfoveal retinal thickness. Of the 129 treatment-emergent adverse events among 32 participants, 49 (38%) were related to minocycline (with no severe or ocular events), including elevated thyrotropin level (15 participants) and skin hyperpigmentation/discoloration (8 participants)., Conclusions and Relevance: In this phase 2 nonrandomized controlled trial, oral minocycline was not associated with a decrease in GA enlargement over 24 months, compared with the run-in phase. This observation was consistent across primary and secondary outcome measures. Oral minocycline at this dose is likely not associated with slower rate of enlargement of GA in AMD.

Background: In women, breast cancer is the second most frequent type of cancer. Looking for new and effective cancer-specific therapies with little to no adverse effects on healthy cells is critical., Objective: Minocycline, a second-generation tetracycline, has shown anticancer effects by targeting multiple pathways in various cancers. This study aimed to determine minocycline effects on the cell proliferation, apoptosis, and invasion of the human MCF-7 cells., Methods: MTT assay was used to evaluate the cytotoxicity of minocycline on the cells. Flow cytometry was performed to investigate the induction of apoptosis and the cell cycle progression. The expression levels of apoptotic and migration proteins and genes were assessed by western blotting and qRT-PCR. The scratch test was performed to evaluate the anti-migration effect of the drug., Results: The results indicated that the IC50 value of minocycline for MCF-7 cells was 36.10 µM. Minocycline treatment caused sub-G1 cell accumulation, indicating a significant apoptotic effect on the MCF-7 cells. Annexin-V/PI staining revealed a significant rise in early and late apoptotic cell percentages. Minocycline up-regulated Bax and Caspase-3 expression and down-regulated Bcl-2 and Pro-Cas3. The scratch test revealed significant anti-migration effects for minocycline. Furthermore, it caused down-regulation of MMP-2 and MMP-9 in a concentration-dependent method., Conclusion: These findings further confirmed the anticancer effect of minocycline and highlighted that minocycline maybe considered as potential therapeutic agent for breast cancer treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Simple hepatic cysts (SHC) are generally asymptomatic and incidentally diagnosed using imaging studies. Asymptomatic SHC does not require treatment, but symptomatic SHC warrants treatment using different modalities, including intravenous antibiotic therapy, ultrasound-guided percutaneous catheter drainage (PCD) with sclerotherapy, and surgery. The dissemination of endoscopic ultrasonography (EUS) intervention techniques has enabled the performance of puncture and drainage via the transgastrointestinal route for intra-abdominal abscesses. Despite the development of an EUS-guided drainage method for treating symptomatic SHC, only a few case reports using this method have been reported. This study retrospectively analyzed the safety and feasibility of EUS-guided drainage of symptomatic SHC as well as its clinical outcomes and compared it with combined therapy using PCD and minocycline sclerotherapy. The records of 10 consecutive patients with 11 symptomatic SHCs treated with either EUS-guided drainage or PCD combined with minocycline sclerotherapy at the Musashino Tokushukai Hospital from August 2019 to January 2024 were retrospectively examined. All cases in both groups achieved technical and clinical success, with no reported adverse events. The median reduction rates of the major cyst diameters in the EUS-guided drainage and PCD with sclerotherapy groups were 100% (interquartile range [IQR]: 94%-100%) and 67% (IQR: 48.5%-85%). The length of hospital stay was 7 and 22.5 days in the EUS-guided and PCD with sclerotherapy groups (P = .01). EUS-guided drainage of symptomatic SHC is a safe and effective therapeutic alternative to percutaneous drainage with sclerotherapy and surgery for treating symptomatic SHC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Venous access device-related bloodstream infection (VAD-BSI) with coagulase-negative staphylococci (CoNS) is a common complication after allogeneic hematopoietic cell transplantation (alloHCT). Standard systemic antimicrobial therapy for uncomplicated VAD-BSI with methicillin-resistant CoNS consists of intravenous (IV) vancomycin (vanco). This requires hospitalization, needs new competent venous access, exposes patients to potential toxicity (mainly renal) and increases the risk of commensal flora dysbiosis with selection of vanco-resistant enterococci. Combined with VAD management (removal or antibiotic locks), oral minocycline (mino) has been evaluated as an alternative systemic therapy for the treatment of uncomplicated VAD-BSIs with CoNS at our center, primarily when the reference treatment with IV vanco was not possible (renal failure or allergy) or when hospitalization was refused by patients. Here, we retrospectively report our single center experience with this mino-based approach., Patients and Methods: From January 2012 to December 2020, 24 uncomplicated VAD-BSIs with CoNS in 23 alloHCT patients were treated with oral mino as systemic antibiotic therapy in combination with VAD management. VAD were implantable ports (n = 17), tunneled catheter (n = 1) or PIC-lines (n = 6). Staphylococci were S. epidermidis (n = 21) or S. haemolyticus (n = 3). Mino was administered with a loading dose of 200 mg followed by 100 mg BID for 7-14 days. For 8 VAD-BSIs, patients were initially treated with IV vanco for the first 1-3 days followed by oral mino, while 16 VAD-BSIs were treated with oral mino as the sole antimicrobial agent for systemic therapy. VAD management consisted of catheter removal (for tunneled catheters and PIC-lines, n = 7) or antibiotic locks with vanco (n = 15) or gentamicin (n = 2) administered at least 3 times a week for 14 days (for ports)., Results: Overall, clearance of bacteremia (as assessed by negativity for the same CoNS of surveillance peripheral blood cultures drawn between day+ 3 and +30 after initiation of systemic therapy) was achieved in all but 1 patient (with port) who had persistent bacteremia at day +9. No complication such as suppurative thrombophlebitis, endocarditis, distant foci of infection or BSI-related death was observed in any patient during the 3-month period after initiation of treatment. Regarding the 17 port-BSI cases for which VAD conservative strategy was attempted, failure of 3-month VAD preservation was documented in 7/17 cases and 3-month recurrence of VAD-BSI was observed in 3/17 cases (with 1 patient with cellulitis). Treatment with mino was well tolerated except for a mild skin rash in one patient., Conclusion: Further prospective studies are needed to evaluate efficacy and safety of this approach., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Masson SAS.)

Introduction: The neuroinflammatory response was seen to impact the formation of phosphorylated tau protein in Alzheimer's disease (AD). This study aims to investigate the molecular mechanism of minocycline in reducing phosphorylated tau protein formation in the hippocampus of lipopolysaccharide (LPS)-induced rats., Methods: Fifty adult male Sprague Dawley (SD) rats were randomly allocated to 1 of 5 groups: control, LPS (5 mg/kg), LPS + minocycline (25 mg/kg), LPS + minocycline (50 mg/kg) and LPS + memantine (10 mg/kg). Minocycline and memantine were administered intraperitoneally (i.p) for two weeks, and LPS was injected i.p. once on day 5. ELISA was used to determine the level of phosphorylated tau protein in SD rats' hippocampal tissue. The density and expression of Toll-like receptor-4 (TLR-4), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кβ), tumour necrosis factor-alpha (TNF-α), and cyclooxygenase (COX)-2 were determined using Western blot and immunohistochemistry., Results: Minocycline, like memantine, prevented LPS-induced increasein phosphorylated tau protein level suggested via reduced density and expression of TLR-4, NF-кβ, TNF-αand COX-2 proteins in rat hippocampal tissue. Interestingly, higher doses were shown to be more neuroprotective than lower doses., Conclusion: This study suggests that minocycline suppresses the neuroinflammation signalling pathway and decreased phosphorylated tau protein formation induced by LPS in a dose-dependent manner. Minocycline can be used as a preventative and therapeutic drug for neuroinflammatory diseases such as AD.

Aims and Objectives: The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions., Method: Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles., Results: In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%)., Conclusion: Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness., (© 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Carbapenem-resistant Acinetobacter baumannii causes one of the most difficult-to-treat nosocomial infections. Polycationic drugs like polymyxin B or colistin and tetracycline drugs such as doxycycline or minocycline are commonly used to treat infections caused by carbapenem-resistant A. baumannii . Here, we show that a subpopulation of cells associated with the opaque/translucent colony phase variation by A. baumannii AB5075 displays differential tolerance to subinhibitory concentrations of colistin and tetracycline. Using a variety of microscopic techniques, we demonstrate that extracellular polysaccharide moieties mediate colistin tolerance to opaque A. baumannii at single-cell level and that mushroom-shaped biofilm structures protect opaque bacteria at the community level. The colony switch phenotype is found to alter several traits of A. baumannii , including long-term survival under desiccation, tolerance to ethanol, competition with Escherichia coli , and intracellular survival in the environmental model host Acanthamoeba castellanii . Additionally, our findings suggest that extracellular DNA associated with membrane vesicles can promote colony switching in a DNA recombinase-dependent manner.IMPORTANCEAs a WHO top-priority drug-resistant microbe, Acinetobacter baumannii significantly contributes to hospital-associated infections worldwide. One particularly intriguing aspect is its ability to reversibly switch its colony morphotype on agar plates, which has been remarkably underexplored. In this study, we employed various microscopic techniques and phenotypic assays to investigate the colony phase variation switch under different clinically and environmentally relevant conditions. Our findings reveal that the presence of a poly N-acetylglucosamine-positive extracellular matrix layer contributes to the protection of bacteria from the bactericidal effects of colistin. Furthermore, we provide intriguing insights into the multicellular lifestyle of A. baumannii , specifically in the context of colony switch variation within its predatory host, Acanthamoeba castellanii ., Competing Interests: The authors declare no conflict of interest.

Background: Growing experimental evidence indicates that cognitive impairment is linked to neuroinflammation. Minocycline (MINO), an antibiotic known for its anti-inflammatory, has shown promise in alleviating cognitive impairment. Nonetheless, the exact mechanism through which MINO improves cognitive impairment is not yet understood., Methods: A neuroinflammatory model was establish by utilizing lipopolysaccharide. The assessment of mice's cognitive and learning abilities was conducted through the MWM and Y-maze tests. The evaluation of hippocampal neuronal injury and microglial activation were achieved by performing HE staining and IHC, respectively. To evaluate BV2 cell viability and apoptosis, the CCK-8 and Hoechst 33342/PI staining assays were employed. In order to assess the protein and RNA expression levels of NLRP3, caspase-1, IL-1β, IL-18, Iba-1, and Bcl2/Bax, WB and RT-qPCR were utilized. Additionally, the inhibitory effect of MINO on apoptosis by targeting the NLRP3/caspase-1 pathway was investigated using Nigericin., Results: MINO was effective in reducing the time it took for mice to escape from the test, increasing the number of platforms they crossed, and mitigating damage to the hippocampus while also suppressing microglial activation and the expression of Iba-1 in a neuroinflammatory model caused by LPS. Furthermore, MINO improved the viability of BV2 cell and reduced apoptosis. It also had the effect of reducing the expression levels of NLRP3/Caspase-1, IL-1β, IL-18, and BAX, while upregulating the expression of Bcl2. Additionally, MINO was found to downregulate the NLRP3 expression, which is specifically activated by nigericin., Conclusion: The protective effect of MINO relies on the crucial involvement of the NLRP3/caspase-1 pathway.

Purpose: This study aimed to investigate whether minocycline could influence alterations of microglial subtypes, the morphology of dendrites and dendritic spines, the microstructures of synapses and synaptic proteins, or even cognition outcomes in immature male mice following status epilepticus (SE) induced by kainic acid., Methods: Golgi staining was performed to visualize the dendrites and dendritic spines of neurons of the hippocampus. The microstructures of synapses and synaptic proteins were observed using transmission electron microscopy and western blotting analysis, respectively. Microglial reactivation and their markers were evaluated using flow cytometry. The Morris water maze (MWM) test was used to analyze spatial learning and memory ability., Results: Significant partial spines increase (predominate in thin spines) was observed in the dendrites of neurons after acute SE and partial loss (mainly in thin spines) was presented by days 14 and 28 post-SE. The postsynaptic ultrastructure was impaired on the 7th and 14th days after SE. The proportion of M1 microglia increased significantly only after acute SE Similarly, the proportion of M2 microglia increased in the acute stage with high expression levels of all surface markers. In contrast, a decrease in M2 microglia and their markers was noted by day 14 post-SE. Minocycline could reverse the changes in dendrites and synaptic proteins caused by SE, and increase the levels of synaptic proteins. Meanwhile, minocycline could inhibit the reactivation of M1 microglia and the expression of their markers, except for promoting CD200R. In addition, treatment with minocycline could regulate the expression of M2 microglia and their surface markers, as well as ameliorating the impaired spatial learning and memory on the 28th day after SE., Conclusions: Dendritic spines and microglia are dynamically changed after SE. Minocycline could ameliorate the impaired cognition in the kainic acid-induced mouse model by decreasing the damage to dendrites and altering microglial reactivation., (© 2023 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Background: The treatment of acne vulgaris is often challenging due to the antibiotic resistance frequently observed in Cutibacterium acnes (C.acnes), a prevalent bacterium linked to this condition., Objective: The objective of this research was to examine the impact of curcumin photodynamic therapy (PDT) on the survival of C.acnes and activity of biofilms produced by this microorganism., Methods: Following the Clinical and Laboratory Standards Institute (CLSI) guidelines, we assessed the drug sensitivity of 25 clinical C.acnes strains to five antibiotics (erythromycin, clindamycin, tetracycline, doxycycline, minocycline) and curcumin by implementing the broth microdilution technique. In addition, we established C.acnes biofilms in a laboratory setting and subjected them to curcumin-PDT(curcumin combined with blue light of 180 J/cm 2 ). Afterwards, we evaluated their viability using the XTT assay and observed them using confocal laser scanning microscopy., Results: The result revealed varying resistance rates among the tested antibiotics and curcumin, with erythromycin, clindamycin, tetracycline, doxycycline, minocycline, and curcumin exhibiting resistance rates of 72 %, 44 %, 36 %, 28 %, 0 %, and 100 %, respectively. In the curcumin-PDT inhibition tests against four representative antibiotic-resistant strains, it was found that the survival rate of all strains of planktonic C. acnes was reduced, and the higher the concentration of curcumin, the lower the survival rate. Furthermore, in the biofilm inhibition tests, the vitality and three-dimensional structure of the biofilms were disrupted, and the inhibitory effect became more significant with higher concentrations of curcumin., Conclusion: The results emphasize the possibility of using curcumin PDT as an alternative approach for the treatment of C.acnes, especially in instances of antibiotic-resistant variations and infections related to biofilms., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)