A randomized, double-blind, positive-controlled, Phase-II clinical trial to evaluate efficacy and safety of Fuke Qianjin capsule in Pakistani patients with pelvic inflammatory disease.

Ethnopharmacological relevance: Pelvic inflammatory disease (PID) is a frequently occurring gynecological disorder mainly caused by the inflammation of a woman's upper genital tract. Generally, antibiotics are used for treating PID, but prolonged use poses potential risks of gut bacterial imbalance, bacterial resistance, super bacteria production, and associated adverse reactions. Traditional Chinese medicine (TCM) has shown unique advantages in various ailments and has received widespread clinical research attention. Fuke Qianjin (FUKE) capsule is an approved National Medical Products Administration (NMPA License No. Z20020024) Chinese herbal prescription that has been widely used individually or in combination with other Western medicines for the treatment of various gynecological inflammatory diseases, including chronic cervicitis, endometritis, and chronic PID. Aim: This clinical trial was designed to assess the safety and efficacy of FUKE capsule in mild-to-moderate symptomatic PID patients. Materials and methods: This phase 2, randomized, double-blind, positive controlled clinical trial was conducted in mild-to-moderate symptomatic PID patients at a single center in Pakistan from 21 September 2021 to 11 March 2022. Eligible female participants were randomly assigned to a test and a control group with a ratio of 1:1. The test group subjects received two metronidazole (METRO) tablets and one doxycycline hyclate (DOXY) simulant at a time, twice daily for 14 days, and two Fuke Qianjin (FUKE) capsules, three times a day after a meal for 28 days. Subjects in the control group received two METRO tablets and one DOXY tablet at a time, twice daily for 14 days, and two FUKE simulant capsules, three times a day after meal for 28 days. The primary efficacy outcome was an improvement in pelvic pain symptoms assessed through a visual analog scale (VAS). The secondary outcomes were the improvement in secondary efficacy symptoms like local physical signs, clinical assessment of leucorrhea and cervical secretions through laboratory examination, and improvement in the maximum area of pelvic effusion assessed through gynecological ultrasound after the treatment. The safety outcomes were assessed through vital signs, laboratory tests, electrocardiogram findings, and adverse events/serious adverse events. Results: A total of 198 subjects with active PID were randomly assigned to a test group (n = 99) and a control group (n = 99). The baseline characteristics of the subjects in the two groups were similar. In the intention-to-treat analysis, the primary efficacy was 84.9% for the test group and 71.6% for the control group, with a statistically significant difference (p = 0.0370; 95% CI -0.2568 to -0.0088). The secondary clinical efficacy was 88.4% for the test group and 82.7% for the control group, with no significant difference (p = 0.2977; 95% CI -0.1632 to 0.0501). The improvement in local physical signs was 95.8% for the test group and 76.9% for the control group, with no significant difference (p = 0.0542; 95% CI -0.3697 to -0.0085). The inter-group non-inferiority comparison showed that the upper limit of the 95% CI was less than 0.15 and thus met the non-inferiority requirements of the test group to the control group. The results of clinical signs of leucorrhea and cervical secretions showed that there was no difference in the rate of improvement between the test and control groups, indicating that FUKE was non-inferior to DOXY. A total of 14 adverse events in eight subjects were observed in the trial, with an incidence rate of 4.7%. Four subjects in each group experienced seven adverse events with 4.5% and 4.8% incidence rates of adverse reactions in the test and control groups, with no statistically significant differences (p = 0.2001). No serious adverse events occurred in the trial. Conclusion: The results of this trial indicate that the test drug (Fuke Qianjin capsule) is non-inferior to the control drug (doxycycline hyclate tablet) in treating mild-to-moderate PID patients with comparable efficacy, safety, and tolerability to the control drug. Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT04723069.

Efficacy of doxycycline therapy for macrolide-resistant Mycoplasma pneumoniae pneumonia in children at different periods.

BACKGROUND: The prevalence of macrolide-resistant Mycoplasma pneumoniae has increased considerably. Treatment in children has become challenging. This study aimed to evaluate the efficacy of doxycycline therapy for macrolide-resistant Mycoplasma pneumoniae pneumonia in children at different periods. METHODS: We retrospectively analyzed the data of patients with macrolide-resistant Mycoplasma pneumoniae pneumonia hospitalized between May 2019 to August 2022. According to treatment, patients were divided into three groups: oral doxycycline treatment alone (DOX group), changed from intravenous azithromycin to oral doxycycline (ATD group), and intravenous azithromycin treatment alone (AZI group). ATD group cases were separated into two sub-groups: intravenous azithromycin treatment<3 days (ATD1 group) and ≥ 3 days (ATD2 group). Clinical symptoms were compared in each group and adjusted by Propensity score matching (PSM) analysis. RESULTS: A total of 106 were recruited in this study. 17 (16%) were in DOX group, 58 (55%) in ATD group, and 31(29%) in AZI group. Compared with ATD group and AZI group, the DOX group showed shorter hospitalization duration and fever duration after treatment, while higher rate of chest radiographic improvement. After using PSM analysis, shorter days to hospitalization duration (P = 0.037) and to fever duration after treatment (P = 0.027) in DOX + ATD1 group than in ATD2 group was observed. A higher number of patients in the DOX + ATD1 group achieved defervescence within 72 h (P = 0.031), and fewer children received glucocorticoid adjuvant therapy (P = 0.002). No adverse reactions associated with doxycycline was observed during treatment. CONCLUSIONS: Children receiving early oral doxycycline had a shorter duration of fever and hospitalization in macrolide-resistant Mycoplasma pneumoniae patients.

Non-steroidal Anti-inflammatory Drug (NSAID)-, Potassium Supplement-, Bisphosphonate-, and Doxycycline-Mediated Peptic Ulcer Effects: A Narrative Review.

Peptic ulcers are a common condition that arises from an imbalance between acid production and gastroduodenal protective factors. Various drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), potassium supplements, bisphosphonates, and doxycycline, can increase the development of peptic ulcers. NSAIDs are one of the most common medications prescribed for pain relief, and they also inhibit the formation of cyclooxygenase-1 (COX-1). COX-1 helps in the production of mucus that lines the stomach, so by inhibiting COX-1, NSAIDs reduce the mucus produced by the stomach and increase the likelihood of gastric ulcer formation. Additionally, NSAIDs are acidic, and increasing the amount of any acid in the stomach can result in promoting ulcer development. Potassium supplements are used to reduce the effects of hypertension, decrease the development of kidney stones, and treat hypokalemia. The various types of transporters and channels used to move potassium across cell membranes increase hydrogen being pumped, increasing gastric acid production and ulcer formation. Bisphosphonates are used to treat a variety of skeletal disorders that require inhibition of osteoclast activity. Nitric oxide (NO) has been shown to have a therapeutic effect on gastric ulcers, and some bisphosphonates have been shown to decrease the production of nitric oxide, resulting in increased damage to the gastric mucosa. Finally, doxycycline is a broad-spectrum tetracycline antibiotic that is typically used to treat anthrax poisoning, skin lesions, and sexually transmitted diseases. A harmful adverse effect of doxycycline is the formation of peptic and gastric ulcers related to the drug being highly acidic once it has dissolved.

Doxycycline-Loaded Calcium Phosphate Nanoparticles with a Pectin Coat Can Ameliorate Lipopolysaccharide-Induced Neuroinflammation Via Enhancing AMPK.

Neuroinflammation occurs in response to different injurious triggers to limit their hazardous effects. However, failure to stop this process can end in multiple neurological diseases. Doxycycline (DX) is a tetracycline, with potential antioxidant and anti-inflammatory properties. The current study tested the effects of free DX, DX-loaded calcium phosphate (DX@CaP), and pectin-coated DX@CaP (Pec/DX@CaP) nanoparticles on the lipopolysaccharide (LPS)-induced neuroinflammation in mice and to identify the role of adenosine monophosphate-activated protein kinase (AMPK) in this effect. The present study was conducted on 48 mice, divided into 6 groups, eight mice each. Group 1 (normal control), Group 2 (blank nanoparticles-treated), Group 3 (LPS (untreated)), Groups 4, 5, and 6 received LPS, then Group 4 received free DX, Group 5 received DX-loaded calcium phosphate nanoparticles (DX@CaP), and Group 6 received DX-loaded calcium phosphate nanoparticles with a pectin coat (Pec/DX@CaP). At the end of the experimentation period, behavioral tests were carried out. Then, mice were sacrificed, and brain tissue was extracted and used for histological examination, and assessment of interleukin-6 positive cells in different brain areas, in addition to biochemical measurement of SOD activity, TLR-4, AMPK and Nrf2. LPS can induce prominent neuroinflammation. Treatment with (Pec/DX@CaP) can reverse most behavioral, histopathological, and biochemical changes caused by LPS. The findings of the current study suggest that (Pec/DX@CaP) exerts a significant reverse of LPS-induced neuroinflammation by enhancing SOD activity, AMPK, and Nrf2 expression, in addition to suppression of TLR-4.

Efficacy of Doxycycline and Ciprofloxacin for Treatment of Pneumonic Tularemia in Cynomolgus Macaques.

BACKGROUND: The incidence of pneumonic tularemia is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCMs) in humans. The US Food and Drug Administration's Animal Model Qualification Program under the Drug Development Tools Program is a regulatory pathway for animal models used in MCM efficacy testing and approval under the Animal Rule. The National Institute of Allergy and Infectious Diseases and Biomedical Advanced Research and Development Authority worked together to qualify the cynomolgus macaque model of pneumonic tularemia. METHODS: Using the model parameters and end points defined in the qualified model, efficacy of the antibiotics doxycycline and ciprofloxacin was evaluated in separate studies. Antibiotic administration, aimed to model approved human dosing, was initiated at time points of 24 hours or 48 hours after onset of fever as an indicator of disease. RESULTS: Upon aerosol exposure (target dose of 1000 colony-forming units) to Francisella tularensis SchuS4, 80% of vehicle-treated macaques succumbed or were euthanized. Ciprofloxacin treatment led to 10 of 10 animals surviving irrespective of treatment time. Doxycycline administered at 48 hours post-fever led to 10 of 10 animals surviving, while 9/10 animals survived in the group treated with doxycycline 24 hours after fever. Selected surviving animals in both the placebo and doxycycline 48-hour group showed residual live bacteria in peripheral tissues, while there were no bacteria in tissues from ciprofloxacin-treated macaques. CONCLUSIONS: Both doxycycline and ciprofloxacin were efficacious in treatment of pneumonic tularemia, although clearance of bacteria may be different between the 2 drugs.

Comparison of Doxycycline or Minocycline to Sulfamethoxazole-Trimethoprim for Treatment of Stenotrophomonas maltophilia Pneumonia.

BACKGROUND: Stenotrophomonas maltophilia is a multidrug-resistant organism with limited antibiotic treatment options. Minocycline and doxycycline may be appropriate, but clinical data are limited. OBJECTIVE: To compare tetracyclines (minocycline and doxycycline [TCN]) with standard of care, sulfamethoxazole-trimethoprim (TMP-SMZ), in S. maltophilia pneumonia treatment. METHODS: This retrospective, 2-center study evaluated patients treated for S. maltophilia pneumonia with TCN or TMP-SMZ for clinical success, defined as resolution of leukocytosis, fever, and tachypnea. Patients were classified as treatment with TCN or TMP-SMZ based on definitive agent used for ≥50% of the treatment course and ≥4 days. Inclusion criteria were age ≥18 years, S. maltophilia confirmed on respiratory culture from January 2013 to November 2020, and appropriate definitive antibiotic dosing. Pregnancy, incarceration, S. maltophilia-resistant or intermediate to definitive therapy, and combination therapy for treatment of S. maltophilia pneumonia were exclusion criteria. Secondary outcomes were microbiologic success and recurrence or reinfection within 30 days requiring treatment. RESULTS: A total of 80 patients were included (21 TCN [15 minocycline, 6 doxycycline], 59 TMP-SMZ). There was no difference in clinical success (28.6% vs 25.4%; P = 0.994), microbiologic success (n = 28, 55.6% vs 66.4%; P = 0.677), or recurrence or reinfection (n = 24, 66.7% vs 26.7%; P = 0.092) between TCN and TMP-SMZ, respectively. CONCLUSION AND RELEVANCE: Clinical and microbiologic success rates were similar in patients treated with TCN compared with TMP-SMZ for S. maltophilia pneumonia. These data suggest minocycline and doxycycline may be options to treat S. maltophilia pneumonia, but conclusive clinical data continue to be lacking.

Selenium Deficiency Promotes Dilatation of the Aorta by Increasing Expression and Activity of Vascular Smooth Muscle Cell Derived Matrix Metalloproteinase-2.

OBJECTIVE: Selenium (Se) is a key part of the body's oxidation defence system. However, it is unclear whether Se affects the development of aortic aneurysm (AA). An animal experiment was conducted to clarify the role of Se in AA development. METHODS: C57BL/6N male mice were fed with a Se deficient (Se-D, < 0.05 mg/kg), Se adequate (Se-A, 0.2 mg/kg), or Se supplemented (Se-S, 1 mg/kg) diet for 8 weeks. Subsequently, an AA murine model (Se-D, n = 11; Se-A, n = 12; Se-S, n = 15) was established using angiotensin II (Ang II, 1 mg/kg/min) for four weeks plus ß-aminopropionitrile (BAPN, 1 mg/mL) for the first two weeks. Saline replaced Ang II, and BAPN was removed during the modelling process for sham mice (Se-A, n = 9). To determine whether Se deficiency promoted aortic dilation via matrix metalloproteinase-2 (MMP-2), the non-specific MMP inhibitor doxycycline (Dox, 100 mg/kg/day) was given to Se-D AA mice (n = 7) for two weeks. RESULTS: The maximum aortic diameter in Se-D AA model mice was significantly increased compared with Se-A AA model mice. MMP-2 expression and activity in the aortic media of Se-D AA model mice was significantly increased compared with Se-A AA model mice. A large number of vascular smooth muscle cells (VSMCs) were found aggregating in the media of the non-dilated aorta of Se-D AA model mice, which was completely inhibited by Dox. The percentage of VSMCs in aortic media of Se-D AA model mice was significantly higher than in Se-A AA model mice. The maximum aortic diameter and occurrence rate of AA in Se-D AA model mice with Dox were significantly reduced compared with Se-D AA model mice. CONCLUSION: Se deficiency promoted dilatation of the aorta in AA model mice by increasing expression and activity of VSMC derived MMP-2, causing abnormal aggregation and proliferation of VSMCs in aortic media.

The formation of Fe3+-doxycycline complex is pH dependent: implications to doxycycline bioavailability.

The interactions of drugs with iron are of interest in relation to the potential effects of iron-rich foods and iron supplements on sorption and bioavailability. Doxycycline (DOX), a member of the tetracycline class of broad-spectrum antibiotics, is frequently administered by oral route. In the digestive tract, DOX can be exposed to iron at different pH values (stomach pH 1.5-4, duodenum pH 5-6, distal jejunum and ileum pH 7-8). In relation to this, we analyzed the impact of pH on Fe3+-DOX complex formation. The optimal conditions for Fe3+-DOX complex formation are pH = 4 and [Fe3+]/[DOX] = 6 molar ratio. HESI-MS showed that Fe3+-DOX complex has 1:1 stoichiometry. Raman spectra of Fe3+-DOX complex indicate the presence of two Fe3+-binding sites in DOX structure: tricarbonylamide group of ring A and phenolic-diketone oxygens of BCD rings. The Fe3+-DOX complex formed at pH = 4 is less susceptible to oxidation than DOX at this pH. The increase of pH induces the decomposition of Fe3+-DOX complex without oxidative degradation of DOX. The pH dependence of Fe3+-DOX complex formation may promote unwanted effects of DOX, impeding the absorption that mainly takes place in duodenum. This could further result in higher concentrations in the digestive tract and to pronounced impact on gut microbiota.

Tetracycline antibiotics: Potential anticancer drugs.

In recent years, research on tetracycline antibiotics has gradually shifted from their antibacterial effects to anticancer effects. Doxycycline, minocycline, and tigecycline as the US Food and Drug Administration (FDA) approved tetracycline antibiotics have been the main subjects of studies. Evidence indicated that they have anticancer properties and are able to control cancer progression through different mechanisms, such as anti-proliferation, anti-metastasis, and promotion of autophagy or apoptosis. In addition, studies have shown that these three tetracycline antibiotics can be utilized in conjunction with chemotherapeutic and targeted drugs to inhibit cancer progression and improve the quality of patient survival. Therefore, doxycycline, minocycline, and tigecycline are taken as examples in this work. Their mechanisms of action in different cancers and related combination therapies are introduced. Their current roles in alleviating the suffering of patients undergoing chemotherapy when used as adjuvant drugs in clinical treatment are also described. Finally, the research gaps and potential research directions at this stage are briefly summarized.

Comparative study evaluating the efficacy of topical azithromycin versus oral doxycycline in the treatment of meibomian gland dysfunction.

Objective: To assess the efficacy of topical azithromycin drops versus oral doxycycline therapy in meibomian gland dysfunction. METHODS: The prospective randomised trial was conducted from December 2019 to June 2020 at the Qazi Hussain Ahmad Medical Complex, Nowshera, Pakistan, and comprised patients of either gender aged 26-42 years having long-standing posterior blepharitis / meibomian gland dysfunction. The subjects were randomised into two equal groups. Both the groups were advised to do warm compresses and lid massage three times a day for 5 min. each for 4 weeks. In addition, group A received azithromycin 1% drops 2 times/day for 1 week, followed by once a day for 3 weeks, while group B received oral doxycycline 100mg once a day for 4 weeks. Baseline, midstream at 2 weeks and post-intervention status, including subjective symptoms, were compared. RESULTS: Of the 60 subjects enrolled, there were 30(50%) in each of the two groups; 32(53.3%) males and 28(46.4%) females. While all 30(100%) the participants in group A completed the trial without any adverse reaction to medication, 8(26.7%) in group B quit midstream owing to anorexia/nausea and gastrointestinal discomfort. Compared to baseline, reduction in both subjective and objective features of the disease in both groups were noted regardless of gender (p=0.08). No significant difference was evident in symptoms healing rate and improvement in foreign body sensation between the groups (p>0.05). Group A treatment improved eye redness, while group B proved better in respect of meibomian glands obstruction healing and corneal staining p<0.05). Conclusion: Both topical azithromycin and oral doxycycline were effective and had their own edge as far as symptomatic improvement was concerned in the treatment of meibomian gland dysfunction.

Baicalein Resensitizes Multidrug-Resistant Gram-Negative Pathogens to Doxycycline.

As multidrug-resistant pathogens emerge and spread rapidly, novel antibiotics urgently need to be discovered. With a dwindling antibiotic pipeline, antibiotic adjuvants might be used to revitalize existing antibiotics. In recent decades, traditional Chinese medicine has occupied an essential position in adjuvants of antibiotics. This study found that baicalein potentiates doxycycline against multidrug-resistant Gram-negative pathogens. Mechanism studies have shown that baicalein causes membrane disruption by attaching to phospholipids on the Gram-negative bacterial cytoplasmic membrane and lipopolysaccharides on the outer membrane. This process facilitates the entry of doxycycline into bacteria. Through collaborative strategies, baicalein can also increase the production of reactive oxygen species and inhibit the activities of multidrug efflux pumps and biofilm formation to potentiate antibiotic efficacy. Additionally, baicalein attenuates the lipopolysaccharide-induced inflammatory response in vitro. Finally, baicalein can significantly improve doxycycline efficacy in mouse lung infection models. The present study showed that baicalein might be considered a lead compound, and it should be further optimized and developed as an adjuvant that helps combat antibiotic resistance. IMPORTANCE Doxycycline is an important broad-spectrum tetracycline antibiotic used for treating multiple human infections, but its resistance rates are recently rising globally. Thus, new agents capable of boosting the effectiveness of doxycycline need to be discovered. In this study, it was found that baicalein potentiates doxycycline against multidrug-resistant Gram-negative pathogens in vitro and in vivo. Due to its low cytotoxicity and resistance, the combination of baicalein and doxycycline provides a valuable clinical reference for selecting more effective therapeutic strategies for treating infections caused by multidrug-resistant Gram-negative clinical isolates.

Sunlight promoted self-fenton photodegradation and pathway of doxycycline: Interactive effects of nanomaterial on bean plant and its genotoxicity against Allium cepa.

Photocatalytic induction of electron/hole recombination, surface property and light response ability effectively enhance the photocatalytic activity of nanomaterial. In this work, the effective charge carrier separating Sn/Mn-ZnFe2O4-CdFe2O4-Ag3PO4 Quantum dots (M/SZFO-CFO-AP QDs) was fabricated for photocatalytic degradation of doxycycline (doxy) antibiotic. The result showed enhanced photocatalytic activity of doxy and the degradation efficiency of doxy was about 98.8% in short span of time. The calculated WH plot and urbach energy of prepared photocatalyst exhibited evidence for the prevalence of point defects and its contribution to efficient charge separation and transferability. The total organic carbon (TOC) removal was found to be 98.9%, which depicts the complete mineralization of doxy. The synergetic charge transfer of n-p-n heterojunction enables the effective removal of doxy under visible light irradiation. Further, the genotoxicity study was determined by interacting the SZFO-CFO-AP QDs with Allium Cepa. The results depict that SZFO-CFO-AP QDs show lower toxicity level and there were no trace of defective mitotic phases and micro nuclei. Further, the progression and development of bean plant was determined after treating with prepared nanomaterials and the result showed the enhanced growth in SZFO-CFO-AP QDs treated bean plant compared to the counterparts. Therefore, the prepared SZFO-CFO-AP QDs was can be used as an environmental friendly photocatalyst for effective treatment of antibiotic present in the water bodies.

Montelukast as an effective adjuvant in the treatment of moderate acne vulgaris.

Although antibiotics are among the most commonly used treatments of acne, there are refractory cases, or they can cause some complications. Recently, leukotriene B4 has been found to play a major role in inflammatory acne lesions. This double blind, randomized clinical trial was conducted on 108 patients with acne who needed systemic therapy and referred to dermatology clinics affiliated to Shiraz University of Medical Sciences. One group (53 patients) received 100 mg doxycycline daily plus placebo and the other group (55 patients) received 100 mg daily doxycycline plus 10 mg daily montelukast. Both groups also received topical benzoyl peroxide 5% every other night. The study period was 3 months and the patients were investigated by lesion count, investigator global assessment (IGA), global acne grading system (GAGS), and Cardiff acne disability index (CADI) scoring systems. Total lesion count, inflammatory lesion count, and non-inflammatory lesion count as well as IGA and GAGS decreased in both treatment groups. At the end of the study, however, the inflammatory lesion count and IGA score reduced more significantly in the montelukast group (p = 0.018 and 0.045, respectively). In addition, the two groups were significantly different with regard to the percentage of decrease in the total lesion count, inflammatory lesions, and IGA (p = 0.033, 0.003, and 0.044, respectively). Thus, montelukast can be used as an adjuvant therapy besides other treatments of acne, especially for inflammatory lesions.

Green synthesis of two-electron centre based ZnO/NiCo2S4 QDs-OVs using Punica granatum fruit peel extract for an exceptional visible light photocatalytic degradation of doxycycline and ciprofloxacin.

Biosynthesis of nanomaterials using plant extract makes them attractive in the field of photocatalysis as they are environmental friendly. The current study focused on the biosynthesis of ZnO/NiCo2S4 QDs (NCs) using Punica granatum fruit peel extract as the reducing agent. The nanomaterials were characterized with XRD, FTIR, Raman, SEM, TEM, UV-vis DRS, BET, PL, EIS, and ESR analysis and were used for photocatalytic degradation of doxycycline (DOX) and ciprofloxacin (CIP). The bandgap of ZnO is 3.2 eV, and the decoration of NiCo2S4 QDs aids in narrowing the bandgap (2.8 eV), making the NCs visible light active. The fabricated NCs achieved 99 and 89% degradation of DOX and CIP respectively. The photocatalytic efficiency of ZnO/NiCo2S4 QDs was much higher compared to individual ZnO and NiCo2S4 QDs. The half-life period of DOX and CIP were evaluated to be 58 and 152 min respectively. The percentage of TOC removal in the photodegraded product of DOX and CIP was estimated to be 99 and 89% respectively, indicating the mineralization of the compounds. The enhanced photocatalytic efficiency of the NCs was attributed to the narrowed visible light active bandgap, synergistic charge transfer across the interface, and lower charge recombination. The intermediates formed during the photocatalytic degradation of DOX and CIP were analyzed using GC-MS/MS analysis, and the photodegradation pathway was elucidated. Also, the toxicity of the intermediates was computationally analyzed using ECOSAR software. The fabricated ZnO/NiCo2S4 QDs have excellent stability and reusability, confirmed by XRD and XPS analysis. The reusable efficiency of the NCs for the photocatalytic degradation of DOX and CIP were 98.93, and 99.4% respectively. Thus, the biologically fabricated NCs are shown to be an excellent photocatalyst and have wide applications in environmental remediation.

Ecotoxicological effects of untreated pig manure from diets with or without growth-promoting supplements on Eisenia andrei in subtropical soils.

This study aimed to evaluate the effects of untreated pig manure from diets incorporating growth-promoting supplements (antibiotics and Zn oxide) on the survival and reproduction of Eisenia andrei earthworms. The tested manures were obtained from four different groups of pigs fed with four different diets: CS, a diet based on corn and soymeal; TR, a diet based on corn, soymeal, and ground wheat (15%); CSa, a diet based on corn and soymeal + 100 ppm of doxycycline + 50 ppm of colistin + 2500 ppm of Zn oxide; and TRa, a diet based on corn, soymeal, and ground wheat (15%) + 100 ppm of doxycycline + 50 ppm of colistin + 2500 ppm of Zn oxide. The study used two soils representative of the Southern region of Brazil (Oxisol and Entisol). In general, there were no significant differences between the different manures tested in each soil. However, there were differences in the toxicity manure on E. andrei between the soils, and the magnitude of this effect was dependent on the applied dose. In Oxisol, LC50 values were higher than 80 m3 ha-1, and EC50 varied from 9 to 27 m3 ha-1. In Entisol, the LC50 values were below the lowest dose tested (< 25 m3 ha-1), and EC50 remained around 5 m3 ha-1. It may be possible that the effects observed were attributed to an excess of nitrogen, copper, and zinc, promoted by the addition of the untreated manure and how these factors interacted with soil type.

Terapêutica adjuvante na modulação da resposta imune no tratamento da doença periodontal: uma revisão de literatura / Adjuvant therapeutic in the modulation of the immune response in the treatment of periodontal disease: a literature review

Introdução: A Doença Periodontal tem caráter multifatorial, já que depende de condições microbiológicas, imunogenéticas e sistêmicas do hospedeiro. Representa inflamação crônica das estruturas de suporte e proteção dental. Desencadeia uma complexa estimulação imunológica, bem como a produção de citocinas inflamatórias, que mediam a destruição óssea e de tecido conjuntivo, provocando perda dental e complicações à distância. A compreensão da etiopatogênese, permitiu os conceitos de modulação, que referem-se às modificações dos aspectos danosos da resposta inflamatória. Objetivo: O presente artigo tem como objetivo realizar uma revisão dos estudos sobre as principais terapêuticas adjuvantes na modulação da resposta imune frente à doença periodontal. Revisão de Literatura: Foi realizada uma revisão da literatura, onde foram selecionados artigos científicos em inglês, publicados entre os anos 2005 a 2020, por meio das bases de dados PubMed e ScienceDirect. No decorrer das buscas, foram utilizadas as palavraschaves "Inflamation", "Periodontal Disease", "Subantimicrobial Dose of Doxycycline", "Periodontal Disease", "Host Response Modulation". Resultados e Conclusão: A literatura é bem promissora em relação à terapia de controle complementar da doença periodontal. Dessa forma, novas pesquisas nessa área podem trazer inúmeros beneficos aos pacientes, sendo, assim, um novo caminho para o contorno da resistência bacteriana(AU)

Introduction: Periodontal disease has a multifactorial character, depending on the host's microbiological, immunogenetic and systemic conditions. It represents chronic inflammation of dental support and protection structures. It triggers a complex immune stimulation, as well as the production of inflammatory cytokines, which mediate bone and connective tissue destruction, causing tooth loss and complications at a distance. The understanding of etiopathogenesis allowed the concepts of modulation, which refers to the modifications of the harmful aspects of the inflammatory response. This article has the escape of conducting a review of studies on the main mechanisms of modulation against periodontal disease. Objective: This article aims to rev iew the studies on the main modulation mechanisms in the face of periodontal disease. Literature Review: A literature review was carried out in which scientific articles were selected in English, published between 2005 and 2020, through the PubMed and ScienceDirect databases. During the searches, the keywords "Inflammation", "Periodontal Disease", "Subantimicrobial Dose of Doxycycline", "Periodontal Disease", "Host Response Modulation". Results and Conclusion: The literature is very promising with complementary control therapy for periodontal disease. Thus, new research in this area can bring countless benefits to patients, thus being a new way to bypass bacterial resistance(AU)

Percutaneous image-guided treatment of aneurysmal bone cysts: is there a superior treatment option?

BACKGROUND: Aneurysmal bone cysts (ABCs) are often treated with intralesional surgery (curettage) with or without adjuvant treatments. Side effects and conflicting results regarding recurrence rates do not suggest one clearly superior therapy. Percutaneous therapeutic options including sclerotherapy and thermal ablation have gained popularity as potential alternatives. OBJECTIVE: The purpose of this retrospective review is to report this institution's experience and results of various image-guided minimally invasive treatments in a single institution series of cases referred to interventional radiology by orthopedic surgery after surgical failure or in patients with anatomically challenging ABCs. MATERIALS AND METHODS: This study identified all patients ≤18 years old who received percutaneous therapy for an ABC, including cryoablation, doxycycline sclerotherapy, microwave ablation or a combination of these modalities. Procedural details, complications, imaging follow-up and clinical follow-up were analyzed. RESULTS: A total of 21 patients received 41 procedures, with major complications seen in 7.7% (3/39) of procedures involving cryoablation or doxycycline sclerotherapy. Patients receiving cryoablation required an average of 1.7 procedures (median: 1 procedure, range: 1-4 procedures) while patients receiving doxycycline sclerotherapy required an average of 3 procedures (median: 2 procedures, range: 1-6 procedures). Patients were followed clinically and with computed tomography or magnetic resonance imaging (average: 23.9 months, range: 3.9-68.3 months). Follow-up imaging demonstrated improvement in 17 (85%) patients. Clinically, 93.8% (15/16) of patients who presented with fracture or pain had markedly reduced or absent pain as well as no fractures. CONCLUSION: Percutaneous image-guided treatment of ABCs demonstrates a favorable efficacy and safety profile. Adding cryoablation may lead to fewer total procedures than using doxycycline sclerotherapy alone.

In Situ Effects of Doxycycline on Neuromuscular Junction in Mice.

BACKGROUND: The antibacterial mechanism of doxycycline is known, but its effects on the nerve-muscle system are still not unclear. OBJECTIVE: The aim of the study was to combine molecular targets of the neuromuscular machinery using the in situ neuronal blocker effect of doxycycline, a semisynthetic second-generation tetracycline derivative, on mice neuromuscular preparations. METHODS: The effects of doxycycline were assessed on presynaptic, synaptic cleft, and postsynaptic neurotransmission, along with the muscle fiber, using the traditional myographic technique. Precisely, the effects of doxycycline were categorized into "all" or "nothing" effects depending on the concentration of doxycycline used; "all" was obtained with 4 µM doxycycline, and "nothing" was obtained with 1-3 µM doxycycline. The rationale of this study was to apply known pharmacological tools against the blocker effect of 4 µM doxycycline, such as F55-6 (Casearia sylvestris), CaCl2 (or Ca2+), atropine, neostigmine, polyethylene glycol (PEG 400), and d-Tubocurarine. The evaluation of cholinesterase enzyme activity and the diaphragm muscle histology were performed, and protocols on the neuromuscular preparation submitted to indirect or direct stimuli were complementary. RESULTS: Doxycycline does not affect cholinesterase activity nor causes damage to skeletal muscle diaphragm; it acts on ryanodine receptor, sarcolemmal membrane, and neuronal sodium channel with a postjunctional consequence due to the decreased availability of muscle nicotinic acetylcholine receptors. CONCLUSION: In conclusion, in addition to the neuronal blocker effect of doxycycline, we showed that doxycycline acts on multiple targets. It is antagonized by F55-6, a neuronal Na+-channel agonist, and Ca2+, but not by neostigmine.

Doxycycline Ameliorates the Severity of Experimental Proliferative Vitreoretinopathy in Mice.

After successful surgeries for patients with rhegmatogenous retinal detachment, the most common cause of retinal redetachment is proliferative vitreoretinopathy (PVR), which causes severe vision impairment and even blindness worldwide. Until now, the major treatment for PVR is surgical removal of the epiretinal membrane, while effective treatment to prevent PVR is still unavailable. Therefore, we investigated the potential of doxycycline, an antibiotic in the tetracycline class, to treat PVR using a mouse model. We used the human retinal pigment epithelial cell line, ARPE-19, for in vitro and in vivo studies to test doxycycline for PVR treatment. We found that doxycycline suppressed the migration, proliferation, and contraction of ARPE-19 cells with reduced p38 MAPK activation and total MMP activity. Intravitreal doxycycline and topical tetracycline treatment significantly ameliorated the PVR severity induced by ARPE-19 cells in mice. PVR increased the expression of MMP-9 and IL-4 and p38 MAPK phosphorylation and modestly decreased IL-10. These effects were reversed by doxycycline and tetracycline treatment in the mouse retina. These results suggest that doxycycline will be a potential treatment for PVR in the future.

177Lu-doxycycline as potential radiopharmaceutical: electrochemical characterization, radiolabeling, and biodistribution in tumor-bearing mice.

PURPOSE: Recent studies with doxycycline as adjuvant therapy to conventional chemotherapy have shown promising results in cancer therapy. The current study aimed to examine the capability of 177Lu-labeled tetracycline ligand, doxycycline hyclate, to use as an anticancer agent. MATERIALS AND METHODS: Doxycycline was radiolabeled with beta-emitting radioisotope 177Lu. Complex formation and its interaction with DNA were investigated electrochemically. Binding of 177Lu-doxycycline to CT 26 cell line was done. Biodistribution of 177Lu-doxycycline was examined in healthy Wistar rats and CT26 colon carcinoma tumor-bearing mice by i.v. and i.p. administration, respectively. RESULTS: Doxycycline hyclate was successfully radiolabeled with 177Lu in high radiolabeling yield (>99%). The radiolabeled complex was stable in vitro in saline and human serum over 72 h. Non-radioactive Lu-doxycycline complex formation was demonstrated electrochemically as well. Intercalative interactions of the doxycycline and Lu-doxycycline with DNA were proved using simultaneously spectrophotometric and electrochemical methods. The binding of the radiolabeled complex with plasma proteins was 4.0 ± 0.4%. The partition coefficient showed the lipophilic nature of the complex similar to the free ligand. The binding curve demonstrates binding from 0.1 nM concentrations of 177Lu-doxycycline, with half-binding estimated ∼100 nM. Biodistribution studies of 177Lu-doxycycline in CT26 colon tumor-bearing mice showed a satisfactory accumulation rate in the tumor (2.88 ± 0.85% ID/g) 3 h after intraperitoneal injection. Both the hepatobiliary system and the urinary system were prominent as excretory routes of the radiolabeled complex. CONCLUSION: Considering obtained results, 177Lu-doxycycline complex, due to its excellent electrochemical and biological characteristics, with emphasis on the binding ability to DNA via intercalative interaction as well as significant accumulation in the tumor, is suitable for further in vivo studies to investigate its potential use in cancer treatment.