Effects Of Minocycline Research Articles

New-generation tetracyclines for severe macrolide-resistant Mycoplasma pneumoniae pneumonia in children: a retrospective analysis

BackgroundMacrolide-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.MethodsThis 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 χ2 or Fisher’s exact tests were used for group comparisons.ResultsA 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).ConclusionDoxycycline 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.

Estrogen receptor α regulates the IKKs/NF-kB activity involved in the development of mechanical allodynia induced by REM sleep deprivation in rats

Several signaling pathways that converge in NF-kB activation have been linked to developing and maintaining different types of pathological pain. In addition, some mechanisms implied in the establishment of chronic pain have been demonstrated to have a sex-dependent correlation. This study aimed to determine if the IKKs/NF-kB signaling pathway is involved in establishing REM sleep deprivation (REMSD) induced mechanical allodynia in rats and its possible regulation depending on estradiol and estrogen receptors. Intrathecal administration of BMS-345541 or minocycline, two drugs that reduce the IKKs/NF-kB activity, avoided the development of mechanical allodynia in female but not in male rats subjected to 48 h of REMSD. Ovariectomy in female rats abolished the effect of BMS-345541 and minocycline. Meanwhile, the 17-β-estradiol restitution restored it. Intrathecal administration of MPP, a selective ERα antagonist, but not PHTPP, a selective ERβ antagonist, avoided the effect of BMS-345541 in female rats without hormonal manipulation. In addition, the transient run-down of ERα in female rats abolished the effect of BMS-345541. All data suggest an important role of ERα as a regulator of the IKKs/NF-kB activity. REMSD increased the ERα protein expression in the dorsal root ganglia and the dorsal spinal cord in females but not in male rats. Interestingly, ERα activation or ERα overexpression allowed the effect of BMS-345541 in male rats. Data suggest an important regulatory role of ERα in the IKKs/NF-kB activity on establishing mechanical allodynia induced by REMSD in female rats.

Antioxidative and cardioprotective effects of minocycline in ischemia/reperfusion injury in experimental model of hypertension.

Cardiovascular diseases remains leading cause of death and disabilities. Coronary artery occlusion and consequent ischemia leads to acute myocardial infarction, but restoration of blood flow, paradoxically, provokes further myocardial damage known as reperfusion injury. Minocycline is possessing anti-inflammatory and anti-apoptotic activity, immune-modulating and antioxidative properties besides its primary antibacterial effect. Recently it gained significant interest in preventing cardiac damage especially due to myocardial ischemia/reperfusion injury (MI/RI). The aim of this study was to assess the protective ability of pre-treatment and post-treatment of isolated hearts from healthy and spontaneously hypertensive rats with minocycline, on functional recovery and redox status after MI/RI using Langendorff technique. Using sensor in the left ventricle, the cardiodynamic parameters were recorded and in the samples of the coronary venous effluent oxidative stress biomarkers were analyzed. Minocycline was injected directly into the coronary vessels, in pre-treatment 5min before global ischemia, and in post-treatment during the first 5min of reperfusion. Changes in redox balance induced by minocycline were more prominent in post-treatment fashion of application. Cardioprotective effects of minocycline due to MI/RI are even more significant in hypertensive hearts. Minocycline showed significant cardioprotective effects, which was more pronounced in hypertensive compared to healthy hearts. Reduction of pro-oxidative biomarkers was more prominent in hypertensive hearts compared to the normotensive, especially if it is applied in the form of post-treatment. Minocycline could be important tool in reduction of heart damage induced by MI/RI due to its antioxidative potential, if these results are confirmed by clinical study.

Safety profiles of tetracycline-class drugs: a pharmacovigilance analysis of the FAERS database

ABSTRACT Background As synthesis technology advances, novel and efficient derivatives of tetracyclines are found. Three new antibiotics were approved within the past 18 years, and represent a new era in the use of tetracyclines. To gain further insight into adverse events linked to tetracyclines and better protect pediatric patients, ongoing monitoring of safety data is crucial. Methods The FAERS data from the first quarter of 2004 to the third quarter of 2023 in the AERSMine were extracted to conduct disproportionality analysis. The association between five tetracyclines and adverse events was evaluated using reporting odds ratio, and their risk factors were explored by multivariate logistic regression analysis. Results Our study showed that thyroid gland disorders had the strongest signal in children. Patients aged 12–18 and treatment with minocycline are risk factors for thyroid adverse events (12–18: OR = 10.727 [7.113–16.177], p < 0.0001; minocycline: OR = 17.025 [10.475–27.678], p < 0.0001). Second-generation tetracycline and third-generation tetracycline ADR patterns differed. Blood fibrinogen decreased and hypofibrinogenaemia was primarily reported with tigecycline and eravacycline. Conclusion This study provided basic evidence for further research on tetracyclines-related adverse events. However, the safety of third-generation tetracycline in children requires additional validation through a large-scale prospective study.

Effect of minocycline on changes in affective behaviors, cognitive function, and inflammation in breast cancer survivors undergoing chemotherapy: a pilot randomized controlled trial

PurposeMinocycline 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.MethodsThis 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.ResultsFifty-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).ConclusionDespite 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.

Minocycline alleviates microglia ferroptosis by inhibiting HO-1 during cerebral ischemia-reperfusion injury.

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. A middle cerebral artery occlusion (MCAO) model was applied to induce CIRI in rats. At 0h, 24h and 48h post-operation, rats were intraperitoneally injected with 45mg/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 72h 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 Fe2+ and ferroptosis-associated gene/protein levels were measured. Hemin was used for further validation after transcriptome analysis. 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 Fe2+ 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. 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.

Minocycline Inhibits Tick-Borne Encephalitis Virus and Protects Infected Cells via Multiple Pathways.

Tick-borne Encephalitis (TBE) is a zoonotic disease caused by the Tick-borne Encephalitis virus (TBEV), which affects the central nervous system of both humans and animals. Currently, there is no specific therapy for patients with TBE, with symptomatic treatment being the primary approach. In this study, the effects of minocycline (MIN), which is a kind of tetracycline antibiotic, on TBEV propagation and cellular protection in TBEV-infected cell lines were evaluated. Indirect immunofluorescence, virus titers, and RT-qPCR results showed that 48 h post-treatment with MIN, TBEV replication was significantly inhibited in a dose-dependent manner. In addition, the inhibitory effect of MIN on different TBEV multiplicities of infection (MOIs) in Vero cells was studied. Furthermore, the transcriptomic analysis and RT-qPCR results indicate that after incubation with MIN, the levels of TBEV and CALML4 were decreased, whereas the levels of calcium channel receptors, such as RYR2 and SNAP25, were significantly increased. MIN also regulated MAPK-ERK-related factors, including FGF2, PDGFRA, PLCB2, and p-ERK, and inhibited inflammatory responses. These data indicate that administering MIN to TBEV-infected cells can reduce the TBEV level, regulate calcium signaling pathway-associated proteins, and inhibit the MAPK-ERK signaling pathway and inflammatory responses. This research offers innovative strategies for the advancement of anti-TBEV therapy.

Effects of Minocycline as a Neuroprotective Agent for Stroke on Mmp-9 Levels, Functional Outcome, and Mortality

Highlights:1. As minocycline plays an important role in stroke microglia activation and iron chelation, it is important to further analyze its effects on stroke treatment.2. This meta-analysis revealed a significant effect of minocycline therapy, as evidenced by improved functional outcomes and inhibited matrix metalloproteinase-9 (MMP-9) activity. Abstract Stroke is the most common and devastating cerebrovascular disease. Many neuroprotective medications, such as scale and minocycline, have been developed to help the nervous system recover or regenerate after a stroke. However, it remains unclear whether minocycline provides a beneficial effect on stroke. We conducted this systematic review and meta-analysis to synthesize the effects of minocycline in stroke treatment. The systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO), with registration number CRD42023485168. The quality of the eligible studies was assessed using the Jadad scale. This systematic review included three ischemic stroke trials, seven intracerebral hemorrhage trials, and one study on acute stroke. There was a significant association between minocycline intervention and stroke severity according to the National Institute of Health Stroke Scale (NIHSS), with a pooled mean difference (MD) of -1.92, a 95% confidence interval (CI) of -3.39 to -0.45, and a value of p=0.01. In the subgroup of ischemic stroke, the modified Rankin Scale (mRS) was significantly lower in the minocycline treatment group compared to the control group (MD=-0.89, 95% CI=-1.54 to -0.25, p=0.007). Additionally, matrix metalloproteinase-9 (MMP-9) levels for the intracerebral hemorrhage subgroup were significantly lower in the minocycline treatment group compared to the control group (MD=-19.93, 95% CI=-36.9 to -2.96, p=0.02). The analysis revealed that minocycline intervention was not significantly associated with hematoma volume, mortality, or stroke recurrence. Our findings indicate that minocycline supplementation is a potential intervention strategy for treating ischemic stroke and intracerebral hemorrhage.

Microglial sex differences in innate high anxiety and modulatory effects of minocycline

Microglia modulate synaptic refinement in the central nervous system (CNS). We have previously shown that a mouse model with innate high anxiety-related behavior (HAB) displays higher CD68+ microglia density in the key regions of anxiety circuits compared to mice with normal anxiety-related behavior (NAB) in males, and that minocycline treatment attenuated the enhanced anxiety of HAB male. Given that a higher prevalence of anxiety is widely reported in females compared to males, little is known concerning sex differences at the cellular level. Herein, we address this by analyzing microglia heterogeneity and function in the HAB and NAB brains of both sexes. Single-cell RNA sequencing revealed ten distinct microglia clusters varied by their frequency and gene expression profile. We report striking sex differences, especially in the major microglia clusters of HABs, indicating a higher expression of genes associated with phagocytosis and synaptic engulfment in the female compared to the male. On a functional level, we show that female HAB microglia engulfed a greater amount of hippocampal vGLUT1+ excitatory synapses compared to the male. We moreover show that female HAB microglia engulfed more synaptosomes compared to the male HAB in vitro. Due to previously reported effects of minocycline on microglia, we finally administered oral minocycline to HABs of both sexes and showed a significant reduction in the engulfment of synapses by female HAB microglia. In parallel to our microglia-specific findings, we further showed an anxiolytic effect of minocycline on female HABs, which is complementary to our previous findings in the male HABs. Our study, therefore, identifies the altered function of synaptic engulfment by microglia as a potential avenue to target and resolve microglia heterogeneity in mice with innate high anxiety.

Decreased hippocampal microglial cell activation by methanolic extract from the leaves of Mallotus oppositifolius (Geiseler) Müll. Arg contributes to its antidepressant-like effect

Background Natural remedies with neuroprotective effect are useful in neuroinflammation-associated depression. Although Mallotus oppositifolius extract (MOE) has previously demonstrated antidepressant and anti-inflammatory properties, its neuroprotective effect remains unknown. Thus, the study evaluated the effect of MOE on lipopolysaccharide (LPS)-induced neuroinflammation-associated depression in mice. Methods Antidepressant-like effect of MOE (10 – 100 mg/kg), fluoxetine (20 mg/kg) and minocycline (50 mg/kg) was established in naïve Institute of Cancer Research (ICR) mice using the forced swim (FST), tail suspension (TST) and open-space swim (OSST) tests. In a separate experiment, FST and TST were used to assess the effect of an 11-day pre-treatment with MOE (10 – 100 mg/kg) or minocycline (50 mg/kg) on LPS (1 mg/kg) neuroinflammation at 6 and 24 hours post LPS. Following these tests, mice were sacrificed and their hippocampi isolated to evaluate their resting and activated microglial cells using Golgi-Cox staining technique. Open-field test was used to assess locomotor activity. Results MOE, fluoxetine and minocycline significantly reduced immobility in FST, TST and OSST compared to vehicle (p &lt; 0.05), confirming their antidepressant-like effect. Interestingly, MOE’s antidepressant-like effect was faster than fluoxetine and minocycline. Conversely, LPS treatment increased immobility behavior at 6 and 24 hours, suggestive of neuroinflammation-induced depression. Compared to vehicle group, pre-treatment with MOE and minocycline ameliorated LPS-induced hippocampal microglial activation and reversed increased immobility behavior without affecting locomotor activity (p &lt; 0.05). Resting microglial cell count was significantly increased by MOE pre-treatment in the OSST-challenged mice compared to vehicle group (p &lt; 0.01). Similarly, MOE pre-treatment reversed LPS-induced reduction in resting microglial count, and restored resting microglial count to normal levels compared to LPS naive vehicle group. Conclusions Collectively, the results suggest that MOE exerts neuroprotective effect against LPS-induced neuroinflammation by decreasing the activation of microglia and increasing resting microglial count. This contributes to its antidepressant-like effect.

Spinal microglial M1 polarization contributes paclitaxel-induced neuropathic pain by triggering cells necroptosis.

Paclitaxel (PTX) is a chemotherapeutic agent that is widely used for the treatment of several types of tumors. However, PTX-induced peripheral neuropathy (PIPN) is an adverse effect generally induced by long-term PTX use that significantly impairs the quality of life. Necroptosis has been implicated in various neurodegenerative disorders. Necroptosis of dorsal root ganglion neurons triggers the pathogenesis of PIPN. Therefore, the present study aims to investigate the role of spinal neuronal necroptosis in PIPN. It also explores the potential role of microglial polarization in necroptosis. We established rat models of PIPN via quartic PTX administration on alternate days (accumulated dose: 8 mg/kg). PTX induced obvious neuronal necroptosis and upregulated the expression of receptor-interacting protein kinase (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the spinal dorsal horn. These effects were inhibited with a necroptosis pathway inhibitor, necrostatin-1 (Nec-1). The effect of microglial polarization on the regulation of spinal necroptosis was elucidated by administering minocycline to inhibit PTX-induced M1 polarization of spinal microglia caused by PTX. We observed a significant inhibitory effect of minocycline on PTX-induced necroptosis in spinal cord cells, based on the downregulation of RIP3 and MLKL expression, and suppression of tumor necrosis factor-α and IL-β synthesis. Additionally, minocycline improved hyperalgesia symptoms in PIPN rats. Overall, this study suggests that PTX-induced polarization of spinal microglia leads to RIP3/MLKL-regulated necroptosis, resulting in PIPN. These findings suggest a potential target for the prevention and treatment of neuropathic pain.

Minocycline mitigated enduring neurological consequences in the mice model of sepsis

AimSepsis-associated encephalopathy is a frequently observed consequence of sepsis, often resulting in chronic brain inflammation and injury, ultimately leading to a range of behavioral abnormalities. This study explores the potential preventive effects of minocycline on the long-lasting outcome of sepsis in a mice model of sepsis. MethodsAdult male C57 mice were subjected to experimental sepsis through a single intraperitoneal injection of 5 mg/kg lipopolysaccharide (LPS). Minocycline administration via oral gavage (12.5, 25, and 50 mg/kg) commenced three days before sepsis induction and continued on the day of induction. Mice underwent behavioral assessments one month post-sepsis, with subsequent brain tissue analysis to investigate oxidative stress markers and cholinergic function. Key findingsOne month following sepsis induction, mice exhibited significant anxiety- and depressive-like behaviors as determined by assessments in the elevated plus maze (EPM), open field, and tail suspension test (TST). Additionally, they displayed impaired recognition memory in the novel object recognition (NOR) test. Brain tissue analysis revealed a notable increase in oxidative stress markers and acetylcholinesterase (AChE) activity in septic mice. Notably, minocycline treatment effectively mitigated the long-term behavioral abnormalities resulting from sepsis, attenuated oxidative stress markers, and reduced AChE activity. SignificanceThese findings underscore the potential of minocycline as a therapeutic intervention during sepsis induction to prevent the enduring behavioral and neurological consequences of experimental sepsis.

Effect of minocycline on total oxidant-antioxidant levels and penicillin induced epileptiform activity in rats

Effect of minocycline on total oxidant-antioxidant levels and penicillin induced epileptiform activity in rats

Minocycline reduces alveolar bone loss and bone damage in Wistar rats with experimental periodontitis.

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.

Pathogenetic therapy of rosacea with systemic tetracyclines

The article presents modern data on the pathophysiology of rosacea and diagnostic criteria for dermatosis. The historical aspects of the introduction of systemic tetracyclines into the therapy of rosacea are outlined. The effect of doxycycline and minocycline on the mechanisms of rosacea development is covered in detail, taking into account modern ideas about the pathogenesis of the disease. At the same time, the advantage of minocycline, compared with doxycycline, is noted, which is manifested by a more pronounced anti-inflammatory effect, as well as a higher antibacterial efficacy, which allows the use of low dosages of minocycline and thereby reduces the risk of adverse events, especially from the gastrointestinal tract. The data of various studies are presented, indicating the expediency of prescribing subantimicrobial doses, as well as the results of evaluating the effectiveness and safety of domestic minocycline minoleksin.&#x0D; It has been proven that the effectiveness of tetracyclines is associated with a pathogenetic effect on innate immunity reactions, with a pronounced anti-inflammatory effect, especially minocycline, suppression of a number of microorganisms, which, apparently, are not a key link in the pathogenesis of rosacea, but can be a trigger factor and initiate inflammation. In addition, minocycline most effectively inhibits the activity of metalloproteinases and increases epidermal hydration

Prophylactic Minocycline for Delirium in Critically Ill Patients: A Randomized Controlled Trial

BackgroundDelirium is a potentially severe form of acute encephalopathy. Minocycline has neuroprotective effects in animal models of neurological diseases; however, data from human studies remain scarce. Research QuestionDoes the neuroprotective effect of minocycline prevent delirium occurrence in critical ill patients? Study design and MethodsThis study was a randomized, placebo-controlled, double-blind trial conducted in four Intensive Care Units (ICUs). Patients aged 18 years or older were eligible and randomized to receive minocycline (100 mg twice a day) 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 different inflammatory (interleukin-1β, interleukin-6, interleukin-10, and C-reactive protein) and brain-related biomarkers (brain-derived neurotrophic factor and S-100B) were used as exploratory outcomes. ResultsA total of 160 patients were randomized, but one patients on the placebo group died before treatment, thus 159 patients were analyzed (minocycline, n=84; placebo, n=75). After the COVID-19 pandemic it was decided to early stop patient inclusion. There was a small but significant decrease in delirium incidence (17 (20%) patients in the minocycline arm compared to 26 (35%) patients in the placebo arm, P=0.043). No other delirium-related outcomes were modified by minocycline treatment. Unexpectedly, there was a significant decrease in hospital mortality (39% vs. 23%, P=0.029). Among all analyzed biomarkers, only plasma levels of C-reactive protein decreased significantly after minocycline treatment (F=0.75, P=0.78 within time; F=4.09, P=0.045 group⋅time). InterpretationOur findings in this rather small study signals 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 RegistrationNCT04219735

Anti-apoptotic effects of minocycline on doxorubicin-induced cardiotoxicity in male Wistar rats

Anti-apoptotic effects of minocycline on doxorubicin-induced cardiotoxicity in male Wistar rats

Effect of minocycline in COVID-19 patients: A randomized clinical trial

Introduction: Minocycline a semi-synthetic tetracycline is a potential therapeutic option for COVID-19 because of its anti-inflammatory and immunomodulatory effects. Moreover, its antioxidant, antiviral, and antiapoptotic effects have been proven. In this study, the efficacy of minocycline in the therapy of COVID-19 patients has been evaluated. Methods: A randomized double-blind placebo-controlled clinical trial was performed in Mashhad, Iran. 40 outpatients were randomized to either the treatment with the minocycline group or the placebo group, in a 1:1 ratio with 20 patients in each group. The Iranian National COVID-19 Therapy Regimen at the time was used in both groups and patients in the treatment group also received oral minocycline 100 mg twice day for 14 days. Patients in both groups were followed on days 3, 7, and 14 after initiating therapy for clinical symptom improvement, improvement of lymphocytes, leukocytes, C-reactive protein (CRP) and SpO2. Results: A total of 40 patients with similar demographic and disease characteristics were enrolled. Results showed that the time interval until clinical symptoms improvement was significantly reduced in the minocycline group (6.85±0.79, day) compared to the placebo (10.95±1.18, day) group (P=0.006). Moreover, the time interval until leukocytes reaching normal limits was significantly reduced in the minocycline group (3.95±0.59, day) compared to the placebo (6.72±1.25, day) group (P=0.046). Conclusion: In this randomized double-blind placebo-controlled study, minocycline (100 mg, BID for 14 days) reduced the duration of clinical symptoms improvement as well as the duration of white blood cell (WBC) normalizing in outpatients of COVID-19 disease.

Effect of minocycline, methyl prednisolone, or combination treatment on the colonic bacterial population in a state of colonic inflammation using the murine dextran sulfate sodium model

BackgroundSeveral reports demonstrated anti-inflammatory properties of minocycline in various inflammatory disorders including colitis. We have experimental evidence suggesting synergistic anti-inflammatory effect of minocycline with methyl prednisolone in reducing colitis severity in mice, but if this effect is in part related to modulating the composition of colonic microbiota is still unknown.Methodsthe effect of vehicle (V), minocycline (M), methyl prednisolone (MP), or combination (C) regimen on the composition of the microbiota of mice in a state of colon inflammation compared to untreated (UT) healthy mice was determined using 16s metagenomic sequencing, and the taxonomic and functional profiles were summarized.ResultsOverall, the bacterial flora from the phylum Firmicutes followed by Bacteroidota were found to be predominant in all the samples. However, the composition of Firmicutes was decreased relatively in all the treatment groups compared to UT group. A relatively higher percentage of Actinobacteriota was observed in the samples from the C group. At the genus level, Muribaculaceae, Bacteroides, Bifidobacterium, and Lactobacillus were found to be predominant in the samples treated with both drugs (C). Whereas “Lachnospiraceae NK4A136 group” and Helicobacter in the M group, and Helicobacter in the MP group were found to be predominant. But, in the UT group, Weissella and Staphylococcus were found to be predominant. Eubacterium siraeum group, Clostridia vadinBB60 group, Erysipelatoclostridium and Anaeroplasma genera were identified to have a significant (FDR p < 0.05) differential abundance in V compared to C and UT groups. While at the species level, the abundance of Helicobacter mastomyrinus, Massiliomicrobiota timonensis and uncultured Anaeroplasma were identified as significantly low in UT, C, and M compared to V group. Functional categories related to amino acid, carbohydrate, and energy metabolism, cell motility and cell cycle control were dominated overall across all the samples. Methane metabolism was identified as an enriched pathway. For the C group, “Colitis (decrease)” was among the significant (p = 1.81E-6) associations based on the host-intrinsic taxon set.ConclusionCombination regimen of minocycline plus methyl prednisolone produces a synergistic anti-inflammatory effect which is part related to alternation in the colonic microbiota composition.

A randomised double-blind placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at risk Mental States: The NAYAB study

BackgroundInflammatory mechanisms are thought to contribute to the onset of psychosis in persons with an at-risk mental state (ARMS). We investigated whether the anti-inflammatory properties of minocycline and omega-3 polyunsaturated fatty acids (omega-3), alone or synergistically, would prevent transition to psychosis in ARMS in a randomised, double-blind, placebo-controlled trial in Pakistan. Methods10,173 help-seeking individuals aged 16–35 years were screened using the Prodromal Questionaire-16. Individuals scoring 6 and over were interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to confirm ARMS. Participants (n = 326) were randomised to minocycline, omega-3, combined minocycline and omega-3 or to double placebo for 6 months. The primary outcome was transition to psychosis at 12 months. FindingsForty-five (13.8 %) participants transitioned to psychosis. The risk of transition was greater in those randomised to omega-3 alone or in combination with minocycline (17.3.%), compared to 10.4 % in those not exposed to omega-3; a risk-ratio (RR) of 1.67, 95 % CI [0.95, 2.92] p = 0.07. The RR for transitions on minocycline vs. no minocycline was 0.86, 95 % CI [0.50, 1.49] p > 0.10. In participants who did not become psychotic, CAARMS and depression symptom scores were reduced at six and twelve months (mean CAARMS difference = 1.43; 95 % CI [0.33, 1.76] p < 0.01 in those exposed to omega-3. Minocycline did not affect CAARMS or depression scores. InterpretationIn keeping with other studies, omega-3 appears to have beneficial effects on ARMS and mood symptom severity but it increased transition to psychosis, which may reflect metabolic or developmental consequences of chronic poor nutrition in the population. Transition to psychosis was too rare to reveal a preventative effect of minocycline but minocycline did not improve symptom severity. ARMS symptom severity and transition to psychosis appear to have distinct pathogeneses which are differentially modulated by omega-3 supplementation. FundingThe study was funded by the Stanley Research Medical Institute.