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minocycline in the eradication of Helicobacter pylori infection: A systematic review and meta-analysis

World Journal of Gastroenterology 2024年第17期30卷 2354-2368页

作者： Kai Zhou Cai-Ling Li Hua Zhang Bao-Jun Suo Yu-Xin Zhang Xin-Lu Ren Yu-Xin Wang Chang-Min Mi Ling-Ling Ma Li-Ya Zhou Xue-Li Tian Zhi-Qiang Song Department of Gastroenterology Peking University Third HospitalBeijing 100191China

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

关键词： Helicobacter pylori minocycline Eradication Safety Resistance

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Bismuth, esomeprazole, metronidazole, and minocycline or tetracycline as a first-line regimen for Helicobacter pylori eradication: A randomized controlled trial

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中华医学杂志(英文版) 2023年第8期136卷 933-940页

作者： Suo Baojun Tian Xueli Zhang Hua Lu Haoping Li Cailing Zhang Yuxin Ren Xinlu Yao Xingyu Zhou Liya Song Zhiqiang Department of Gastroenterology Peking University Third Hospital 3. Beijing 100191 4. China Digestive Disease Research Center of Peking University Research Center of Clinical Epidemiology China.

Background: Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline forHelicobacter pylori (H.pylori) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens.Methods: This randomized controlled trial was conducted on 434 na?ve patients withH.pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4–8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher’s exact test for categorical variables and Student’st-test for continuous variables.Results: As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >?10.0% (ITT analysis: 181/217 [83.4%]vs. 180/217 [82.9%], with a rate difference of 0.5% [?6.9% to 7.9%]; PP analysis: 177/193 [91.7%]vs. 176/191 [92.1%], with a rate difference of ?0.4% [?5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%]vs. 13/214 [6.1%],P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%]vs. 88/214 [41.1%]) and compliance (195/215 [90.7%]vs. 192/214 [89.7%]) were similar between the two groups.Conclusion:

关键词： Helicobacter pylori minocycline Tetracycline Bismuth quadruple therapy

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Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model

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Journal of Otology 2023年第1期18卷 38-48页

作者： Venkatesan Perumal Arun Reddy Ravula Ningning Shao Namas Chandra Center for Injury Biomechanics Materialsand MedicineDepartment of Biomedical EngineeringNew Jersey Institute of TechnologyNewarkNJ07102USA

Blast injuries are common among the military service members and veterans.One of the devastating effects of blast wave induced TBI is either temporary or permanent hearing loss.Treating hearing loss using minocycline is restricted by optimal drug concentration,route of administration,and its half-life.Therefore,therapeutic approach using novel therapeutic delivery method is in great need.Among the different delivery methods,nanotechnology-based drug delivery is desirable,which can achieve longer systemic circulation,pass through some biological barriers and specifically targets desired sites.The current study aimed to examine therapeutic effect of minocycline and its nanoparticle formulation in moderate blast induced hearing loss rat model through central auditory system.The I.v.administered nanoparticle at reduced dose and frequency than regularly administered toxic dose.After moderate blast exposure,rats had hearing impairment as determined by ABR at 7-and 30-days post exposure.In chronic condition,free minocycline also showed the significant reduction in ABR threshold.In central auditory system,it is found in this study that minocycline nanoparticles ameliorate excitation in inferior colliculus;and astrocytes and microglia activation after the blast exposure is reduced by minocycline nanoparticles administration.The study demonstrated that in moderate blast induced hearing loss,minocycline and its nanoparticle formulation exhibited the optimal therapeutic effect on the recovery of the ABR impairment and a protective effect through central auditory system.In conclusion,targeted and non-targeted nanoparticle formulation have therapeutic effect on blast induced hearing loss.

关键词： minocycline Nanoparticle Hearing loss Blast injury and targeted drug delivery

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Morbihan disease misdiagnosed as senile blepharoptosis and successfully treated with short-term minocycline and ketotifen: A case report

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World Journal of Clinical Cases 2023年第19期11卷 4692-4697页

作者： Jun Na Yan Wu Department of Dermatology Peking University First HospitalBeijing 100034China

BACKGROUND Morbihan disease is a rare skin condition with diagnostic and therapeutic challenges.Facial nonpitting erythematous edema is usually considered to be a characteristic manifestation and diagnostic clue for the Morbihan disease.Treatment of Morbihan disease remains a dilemma due to its long course,poor response,and high recurrence rate.CASE SUMMARY We report the case of a 69-year-old man with Morbihan disease.The patient presented ptosis as the first and main symptom.There was no obvious edema or other skin lesions.The patient was misdiagnosed with senile blepharoptosis based on eyelid performance and no treatment was administered to him.After continuous progressive asthenia of eye-opening and ptosis for more than one year,a skin biopsy was recommended.Histopathological analysis showed edema in the dermis,lymphatic hyperplasia and dilatation,and perivascular lymphocytic infiltration.An obvious increase in toluidine blue-stained mast cells was observed.The patient was finally diagnosed with Morbihan disease.minocycline and ketotifen were prescribed based on the increase of mast cells in skin tissue slices.The patient experienced rapid relief seven days later and complete remission after 40 d from the commencement of the treatment.CONCLUSION Ptosis without obvious swelling could be the only or main clinical manifestation of Morbihan disease in rare conditions.An increase of mast cells was an important therapeutic clue to the rapid and remarkable efficiency of the combination therapy of minocycline and antihistamine.

关键词： Morbihan disease Ptosis minocycline Mast cells Treatment Case report

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minocycline protects retinal ganglion cells after optic nerve crush injury in mice by delaying autophagy and upregulating nuclear factor-κB2

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Chinese Medical Journal 2014年第9期127卷 1749-1754页

作者： Jiao Xiaoling Peng Yuan Yang Liu Department of Ophthalmology Peking University First Hospital Key Laboratory of Vision Loss and Restoration Ministry of Education Beijing 100034 China

Background Currently,no medicine is available that can prevent or treat neural damage associated with optic nerve injury.minocycline is recently reported to have a neuroprotective function.The aims of this study were to exarmine the neuroprotective effect of minocycline on retinal ganglion cells （RGCs） and determine its underlying mechanisms,using a mouse model of optic nerve crush （ONC）.Methods ONC was performed in the left eye of adult male mice,and the mice were randomly divided into minocycline-treated group and saline-treated control group.The mice without receiving ONC injury were used as positive controls.RGC densities were assessed in retinal whole mounts with immunofluorescence labeling of βⅢ-tubulin.Transmission electron microscopy was used to detect RGC morphologies,and Western blotting and real-time PCR were applied to investigate the expression of autophagy markers LC3-Ⅰ,LC3-Ⅱ,and transcriptional factors nuclear factor-κB1 （NF-κB1）,NF-κB2.Results In the early stage after ONC （at Days 4 and 7）,the density of RGCs in the minocycline-treated group was higher than that of the saline-treated group.Electron micrographs showed that minocycline prevented nuclei and mitochondria injuries at Day 4.Western blotting analysis demonstrated that the conversion of LC3-Ⅰ to LC3-Ⅱ was reduced in the minocycline-treated group at Days 4 and 7,which meant autophagy process was inhibited by minocycline.In addition,the gene expression of NF-κB2 was upregulated by minocycline at Day 4.Conclusion The neuroprotective effect of minocycline is generated in the early stage after ONC in mice,partly through delaying autophagy process and regulating NF-κB2 pathway.

关键词： minocycline autophagy LC3 protein nuclearfactor-κB2 p52 subunit retinal ganglion cells optic nerve injury

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minocycline targets multiple secondary injury mechanisms in traumatic spinal cord injury

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Neural Regeneration Research 2017年第5期12卷 702-713页

作者： Robert B.Shultz Yinghui Zhong School of Biomedical Engineering Science and Health Systems Drexel University Philadelphia PA USA

minocycline hydrochloride（MH）, a semi-synthetic tetracycline derivative, is a clinically available antibiotic and anti-inflammatory drug that also exhibits potent neuroprotective activities. It has been shown to target multiple secondary injury mechanisms in spinal cord injury, via its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. The secondary injury mechanisms that MH can potentially target include inflammation, free radicals and oxidative stress, glutamate excitotoxicity, calcium influx, mitochondrial dysfunction, ischemia, hemorrhage, and edema. This review discusses the potential mechanisms of the multifaceted actions of MH. Its anti-inflammatory and neuroprotective effects are partially achieved through conserved mechanisms such as modulation of p38 mitogen-activated protein kinase（MAPK） and phosphoinositide 3-kinase（PI3K）/Akt signaling pathways as well as inhibition of matrix metalloproteinases（MMPs）. Additionally, MH can directly inhibit calcium influx through the N-methyl-D-aspartate（NMDA） receptors, mitochondrial calcium uptake, poly（ADP-ribose） polymerase-1（PARP-1） enzymatic activity, and iron toxicity. It can also directly scavenge free radicals. Because it can target many secondary injury mechanisms, MH treatment holds great promise for reducing tissue damage and promoting functional recovery following spinal cord injury.

关键词： minocycline inflammation anti-oxidant neuroprotection oxidative stress glutamate exitotoxicity cytochrome c P38 MAPK PI3K/Akt calcium influx

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minocycline inhibits the production of the precursor form of nerve growth factor by retinal microglial cells

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Neural Regeneration Research 2013年第4期8卷 320-327页

作者： Xiaochun Yang Xuanchu Duan Department of Ophthalmology Second Xiangya HospitalCentral South University

A rat model of acute ocular hypertension was established by enhancing the perfusion of balanced salt solution in the anterior chamber of the right eye. minocycline （90 mg/kg） was administered intraperitoneally into rats immediately after the operation for 3 consecutive days. Immunofluorescence, western blot assay and PCR detection revealed that the expression of the precursor form of nerve growth factor, nerve growth factor and the p75 neurotrophin receptor, and the mRNA expression of nerve growth factor and the p75 neurotrophin receptor, increased after acute ocular hypertension. The number of double-labeled CD11B- and precursor form of nerve growth factor-positive cells, glial fibrillary acidic protein- and p75 neurotrophin receptor-positive cells glial fibrillary acidic protein- and caspase-3-positive cells in the retina markedly increased after acute ocular hypertension. The above-described expression decreased after minocycline treatment. These results suggested that minocycline inhibited the increased expression of the precursor form of nerve growth factor in microglia, the p75 neurotrophin receptor in astroglia, and protected cells from apoptosis.

关键词： neural regeneration biological factor precursor form of nerve growthfactor p75 neurotrophin receptor minocycline apoptosis nerve growth factor acute ocular hypertension retina photographs-containing paper neuroregeneration

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minocycline inhibits 5-lipoxygenase activation and brain inflammation after focal cerebral ischemia in rats

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Acta Pharmacologica Sinica 2007年第6期28卷 763-772页

作者： Li-sheng CHU~(2,3),San-hua FANG~2,Yu ZHOU~2,Guo-liang YU~2,Meng-ling WANG~2,Wei-ping ZHANG~2,Er-qing WEI~(2,4)~2 Department of Pharmacology,School of Medicine,Zhejiang University,Hangzhou 310058,China ~3 Department of Physiology ZhejiangChinese Medical University Hangzhou 310053,China Department of Pharmacology School of Medicine Zhejiang University Hangzhou China Department of Physiology Zhejiang Chinese Medical University Hangzhou China

Aim:To determine whether the anti-inflammatory effect of minocycline on postis-chemic brain injury is mediated by the inhibition of 5-lipoxygenase (5-LOX)expression and enzymatic activation in rats.Methods:Focal cerebral ischemiawas induced for 30 min with middle cerebral artery occlusion,followed byrepel-fusion.The ischemic injuries,endogenous IgG exudation,the accumulationof neutrophils and macrophage/microglia,and 5-LOX mRNA expression weredetermined 72 h after reperfusion.5-LOX metabolites (leukotriene B4and cysteinylleukotrienes) were measured 3 h after reperfusion.Results:minocycline (22.5and 45 mg/kg,ip,for 3 d) attenuated ischemic injuries,IgG exudation,and theaccumulation of neutrophils and macrophage/microglia 72 h after reperfusion.Italso inhibited 5-LOX expression 72 h after reperfusion and the production ofleukotrienes 3 h after reperfusion,Conclusion:minocycline inhibited postis-chemic brain inflammation,which might be partly mediated by the inhibition of5-LOX expression and enzymatic activation.

关键词： minocycline 5-1ipoxygenase leukotriene focal cerebral ischemia inflammation

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minocycline inhibits neuroinflammation and enhances vascular endothelial growth factor expression in a cerebral ischemia/reperfusion rat model

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Neural Regeneration Research 2008年第10期3卷 1088-1094页

作者： Zhiyou Cai Yong Yan Changyin Yu Jun Zhang Department of Neurology the First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Neurology Chongqing 400016 China Department of Neurology the Affiliated Hospital of Zunyi Medical College Zunyi 563003 Guizhou Province China

BACKGROUND： Brain ischemia involves secondary inflammation, which significantly contributes to the outcome of ischemic insults. Vascular endothelial growth factor （VEGF） may play an important role in the vascular response to cerebral ischemia, because ischemia stimulates VEGF expression in the brain, and VEGF promotes formation of new cerebral blood vessels. minocycline, a tetracycline derivative, protects against cerebral ischemia and reduces inflammation, oxidative stress, and apoptosis. OBJECTIVE： To observe the influence of minocycline on VEGE interleukin-1 beta （IL-119 ）, and tumor necrosis factor alpha （TNF-α） expression in Wistar rats with focal cerebral ischemia/reperfusion injury, and to study the neuroprotection mechanism of minocycline against focal cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING： Randomized, controlled experiment, which was performed in the Chongqing Key Laboratory of Neurology between March 2007 and March 2008. MATERIALS： A total of 36 female, Wistar rats underwent surgery to insert a thread into the left middle cerebral artery. Animals were randomly divided into sham-operation, minocycline treatment, and ischemia/reperfusion groups, with 12 rats in each group. minocycline （Huishi Pharmaceutical Limited Company, China） was dissolved to 0.5 g/L in normal saline. METHODS： A 0.5-1.0 cm thread was inserted into rats from the sham-operation group. Rats in the ischemia/reperfusion group underwent ischemia and reperfusion. The minocycline group received minocycline （50 mg/kg） 12 and 24 hours following ischemia and reperfusion, whereas the other groups received saline at the corresponding time points. MAIN OUTCOME MEASURES： mRNA and protein expression of IL-1β and TNF-α was measured by reverse transcriptase-polymerase chain reaction （RT-PCR） and enzyme linked immnnosorbent assay （ELISA）, respectively. VEGF mRNA and protein expression was examined by RT-PCR, Western blot, and ELISA. RESULTS： minocycline decreased the focal infarct volume. VEGF, IL-1β, and TNF-α expression was u

关键词： cerebral ischemia/reperfusion inflammation minocycline vascular endothelial growth factor

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Antimicrobial activity of linezolid combined with minocycline against vancomycin-resistant Enterococci

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Chinese Medical Journal 2013年第14期126卷 2670-2675页

作者： WU Jing JIANG Tian-tong SU Jian-rong LI Li Department of Clinical Laboratory First Hospital of Fangshan District Beijing 102400 China Department of Clinical LaboratoryBeijing Friendship Hospital Capital Medical University Beijing 100050 China Division of Traditional Chinese MedicineBeijing Friendship Hospital Capital Medical University Beijing 100050 China

Background Vancomycin-resistant Enterococci （VRE） cause serious infections that are difficult to treat. We carried out this study to determine the mutant prevention concentration （MPC） of linezolid when combined with minocycline against VRE strains, to determine the mechanism of drug resistance in vitro, and to provide a theoretical basis for the rational use of drugs against VRE. Methods The minimum inhibitory concentrations （MICs） of linezolid and minocycline against 30 Enterococci （E.） isolates （including 20 VRE strains） were determined by the broth microdilution method. Drug interactions were assessed by the checkerboard microdilution tests and confirmed by time-kill studies. Two vancomycin-susceptible strains N27 and N40 （linezolid MIC, 2 g/ml; minocycline MIC, 4 tJg/ml） and control strains E. faecalis ATCC 29212 and ATCC 51299 were also tested. The MPCs of linezolid and minocycline （alone and combined） were determined using the agar dilution method. Strains showing stable resistance were analyzed by polymerase chain reaction （PCR） amplification of domain V of the 23S rRNA gene. Results Checkerboard titration studies revealed synergistic effects of combination therapy in 26.7% of 30 E. isolates. Antagonism was not observed, The G2576U mutation was detected in stable linezolid-resistant strains of ATCC 29212, N40, and N27 before and after resistance screening, and MIC values increased with the number of G2576U mutations. The MPC of linezolid against E. decreased dramatically when combined with minocycline, and vice versa. Conclusion Linezolid or minocycline alone produce resistant strains; however, their joint use may reduce the MPC of each agent against VRE, thereby decreasing resistant mutants and bacterial infections.

关键词： linezolid minocycline Enterococcus mutation

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