Effective Adjunctive Therapy Research Articles

Apoptosis Induction, Cell Cycle Arrest and Anti-Cancer Potential of Tamoxifen-Curcumin Loaded Niosomes Against MCF-7 Cancer Cells.

Background & Objective:Breast cancer is the most common cancer among women. One of the most effective treatments for breast cancer is chemotherapy, in which specific drugs destroy the mass and its proliferation is inhibited. Chemotherapy is the most effective adjunctive therapy when multiple medications are used concurrently. Also, combining the drugs with nanocarrier has become an important strategy in targeted therapy. This study is designed to assess the apoptosis induction, cell cycle arrest, and anti-cancer potential of Tamoxifen-Curcumin-loaded niosomes against MCF-7 Cancer Cells. Methods:A novel niosomal formulation of tamoxifen-curcumin with Span 80 and lipid to drug ratio of 20 was employed. The MCF-7 cells were cultured and then treated with IC50 value of tamoxifen-curcumin-loaded niosomes, the combination of tamoxifen and curcumin, tamoxifen, and curcumin alone. Flow cytometry, Real-Time PCR, and cell cycle analysis tests were conducted to evaluate the induction of apoptosis.Results:Drug-loaded niosomes caused up-regulation of bax and p53 genes and down-regulation of bcl2 gene. Flow cytometry studies showed that niosomes containing tamoxifen-curcumin increased apoptosis rate in MCF-7 cells compared to the combination of tamoxifen and curcumin owing to the synergistic effect between the two drugs along with higher cell uptake by formulation niosomal. These results were also confirmed by cell cycle analysis. Conclusion:Co-delivery of curcumin and tamoxifen using optimized niosomal formulation revealed that at acidic pH of MCF-7 cancer cells, released drugs from niosomal carriers would be more effective than physiological pH. This feature of niosomal nanoparticles can reduce the side effects of drugs in normal cells. Niosomal nanoparticles might be used as a biological anti-cancer factor in treatment of breast cancer.

Pimavanserin augments the efficacy of atypical antipsychotic drugs in a mouse model of treatment-refractory negative symptoms of schizophrenia

Negative symptoms are a core, pervasive, and often treatment-refractory phenotype of schizophrenia, one which contributes to poor functional outcome, ability to work, pursue educational goals, and quality of life, as well as caretaker burden. Improvement of negative symptoms in some patients with schizophrenia has been reported with some atypical antipsychotic drugs [AAPDs], but improvement is absent in many patients and partial in others. Therefore, more effective treatments are needed, and better preclinical models of negative symptoms are needed to identify them. Sub-chronic [sc] treatment of rodents with phencyclidine [PCP], a noncompetitive N-methyl-d-aspartate [NMDAR] antagonist, produces deficits in social interactions [SI] that have been widely studied as a model of negative symptoms in schizophrenia. Acute restraint stress [ARS] also provides a model of treatment-refractory negative symptoms [TRS] to AAPDs. By themselves, in sc-PCP mice, the AAPDs, risperidone, olanzapine, and aripiprazole, but not the selective 5-HT2AR inverse agonist, pimavanserin [PIM], rescued the SI deficit in sc-PCP mice, as did the combination of PIM with sub-effective doses of each of these AAPDs. These three AAPDs alone did not rescue SI deficit in sc-PCP+ 2 h-ARS mice, indicating these mice were treatment refractory. However, co-administration of PIM with any of the AAPDs significantly restored SI in these mice. PIM may be an effective adjunctive therapy for treating negative symptoms of schizophrenia in some patients who have failed to respond to AAPDs, but further studies are needed.

β3-Adrenoceptor Agonist for the Treatment of Bladder Dysfunction in Children: A Systematic Review and Meta-Analysis.

ß3-adrenergic receptor agonists (ß3 agonists) have been used in treatment of overactive bladder (OAB) and neurogenic detrusor overactivity (NDO) in adults. However, their use in children has only recently been approved by the U.S. Food and Drug Administration for patients with NDO. As in adults, the role of ß3 agonists in children may include conditions such as OAB. This systematic review and meta-analysis aims to understand the intended use, efficacy and safety of ß3 agonists in the pediatric population. A literature search was performed in February 2021 across MEDLINE®, Embase®, Scopus®, the Cochrane Library and ClinicalTrials.gov. No language restrictions were placed. All records describing the clinical use of ß3 agonists in pediatric patients (<18 years of age) were included, regardless of the methodological design or outcomes assessed. The identified records were screened by 2 independent authors. The reporting was compliant with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Data extraction was performed by 2 independent reviewers, blinded to each other's extractions. The data were pooled using the fixed effects model. Of 367 records identified, 8 studies were included in the review (3 prospective and 5 retrospective). ß3 agonists led to improvements in both urodynamics parameters and self-reported outcomes such as incontinence. Commonly reported side effects were headaches (3%‒5.9%), constipation (3.5%‒5.7%), rhinitis/nasopharyngitis (1.7%‒5.8%) and blurred vision (1.7%‒2.9%). Clinically meaningful changes in safety outcomes (blood pressure, heart rate, electrocardiogram-related changes, liver function) were rare. Before and after ß3 agonist use, pooled effect estimates for maximum cystometric capacity for 171 patients were mean difference of +98.84 ml (95% CI 74.72, 122.96); for complete dryness, assessment of 235 patients showed a Peto odds ratio of 8.68 (95% CI 5.22, 14.45). ß3 agonists appear to be a promising, effective and safe alternative/adjunctive therapy in management of pediatric NDO or OAB, with improvements in both objective urodynamics parameters and subjective patient-reported outcomes following their use.

Abstract 14027: National Trends and County-Level Patterns of Prescription for PCSK-9 Inhibitors Among Medicare Beneficiaries in the United States

Introduction: PCSK9i are expensive but effective adjunctive lipid lowering therapies but their uptake in clinical practice has largely remained unknown. Hypothesis: We evaluated national trends and patterns of prescription for PCSK9i among Medicare beneficiaries. Methods: We identified lipid-lowering prescriptions in national Medicare Part D database for 2015-2018. To evaluate county level features associated with PCK9i prescriptions, data was merged with AHRQ sociodemographic measures, public health indices from County Health Ranking, and deprivation rank from Neighborhood Atlas. We evaluated trends and county level variation in proportionate PCK9i prescriptions relative to statins. Results: The number of PCSK9i prescribers increased from 16 in 2015 to 9621 in 2018, representing an increase from 0.01% to 3.0% of statin prescribers. There were 2980 counties with ≥10 statin prescribers in 2018, of which only 161 (5.3%) had any PCSK9i prescriptions. Even among counties with PCK9i use, relative to a median 8762 [IQR 7491-10767] for statin-receiving beneficiaries per 100k population, the rates of use were 6.1 [3.0-12.2] beneficiaries for PCSK9i and 177 [111-264] for ezetimibe. At a county level, proportionate PCSK9i beneficiaries relative to statin significantly correlated with county population (r=0.34), education (r=0.22), younger age (r=0.16), household income (r=0.14), lower prevalence of obesity (r=0.14), and lower deprivation rank (r=0.10). After accounting for sociodemographic and cardiometabolic risk factors in logistic regression, county population, education, lower median age, and lower prevalence of obesity significantly predicted PCK9i use. Conclusion: Despite an increased uptake of PCK9i during 2015-2018, only 3% of statin prescribers nationally use any PCSK9i among Medicare beneficiaries. The use is also restricted to only 5% of US counties, which were affluent, suggesting a need for an evaluation to ensure equitable use.

Clinical efficacy of artificially carbonated water bathing on superficial bacterial folliculitis in dogs.

Bathing with artificially carbonated water is reported to be a valuable therapeutic option for various human skin disorders. To evaluate the clinical efficacy of artificially carbonated water bathing on superficial bacterial folliculitis (SBF) caused by Staphylococcus pseudintermedius (SP) in dogs. Nineteen dogs with SBF from whom SP was isolated from skin lesions were enrolled. Dogs with SBF were allocated randomly to either the artificially carbonated water bathing group or the control group bathed with tap water. The dogs were bathed with the designated water type on day (D)0, D7 and D14. Clinical scores and skin surface pH were evaluated on D0 and D21. Colony forming unit (cfu) assays were performed in vitro to investigate whether the artificially carbonated water affected growth of clinical SP isolates. The mean rate of improvement in the clinical scores was significantly higher in the carbonated water group than in the control group. Dogs bathed with carbonated water exhibited significant decreases in their skin surface pH after bathing; dogs bathed with tap water did not. No dogs experienced significant adverse events. The cfus of SP incubated in vitro with artificially carbonated water did not significantly differ from those incubated with tap water. Bathing with artificially carbonated water might be an effective and safe adjunctive therapy for canine SP-induced SBF.

Inflammaging and Cannabinoids

Aging is a complex phenomenon associated with a wide spectrum of physical and physiological changes affecting every part of all metazoans, if they escape death prior to reaching maturity. Critical to survival, the immune system evolved as the principal component of response to injury and defense against pathogen invasions. Because how significantly immune system affects and is affected by aging, several neologisms now appear to encapsulate these reciprocal relationships, such as Immunosenescence. The central part of Immunosenescence is Inflammaging –a sustained, low-grade, sterile inflammation occurring after reaching reproductive prime. Once initiated, the impact of Inflammaging and its adverse effects determine the direction and magnitudes of further Inflammaging. In this article, we review the nature of this vicious cycle, we will propose that phytocannabinoids as immune regulators may possess the potential as effective adjunctive therapies to slow and, in certain cases, reverse the pathologic senescence to permit a more healthy aging.

Battlefield acupuncture appears to be an effective therapy for pain management

Introduction: The Department of Defense has been training primary care providers in battlefield acupuncture (BFA), a subtype of auricular acupuncture, as an adjunct therapy for pain management. Methods: The objective of this study was to evaluate the effectiveness and safety of BFA for pain management in an outpatient Internal Medicine clinic staffed by resident physicians. The target population for this single-center prospective cohort study were military beneficiaries at a medical treatment facility located at the Wright-Patterson Air Force Base. Participants who met inclusion criteria were treated with BFA in addition to routine standard care for pain (n = 69). The control group was composed of participants who received routine standard care only without BFA (n = 27). Pain was assessed by a self-reported pain scale (0–10) at the time of encounter, immediately after BFA (for the intervention group), then at 24 and 48 h afterwards. Results: Mean pain for the intervention group decreased from 5.45 before BFA to 3.29 immediately following BFA to 2.21 at 24 h and to 2.10 at 48 h (p &lt; 0.001). Thus, at all three post-treatment time points, mean decrease in pain surpassed a two-point reduction, deemed to be a clinically important difference. The BFA group had a greater reduction in pain compared to the no intervention group at 24 h (3.14 vs 0.59, p &lt; 0.001) and at 48 h (3.26 vs 0.96, p &lt; 0.001). Four intervention group participants (6%) reported an adverse reaction (three with pain at the insertion site) or complication (one with superficial infection). Conclusion: BFA provided by Internal Medicine residents appears to be a safe and effective adjunct therapy for pain management in an outpatient setting, but requires further validation by randomized controlled trials.

Modified negative pressure wound therapy as an adjunct to antibiotics in the treatment of orthopaedic infected metalwork

PurposeInfected orthopaedic metalwork is challenging to treat. Negative pressure wound therapy (NPWT) with irrigation is an emerging therapy for infected wounds as an adjunct to antibiotic therapy. The senior author had devised a modified technique to augment its efficacy, utilising high-flow rate irrigation and skin closure over the standard NPWT dressing. This novel technique was originally evaluated in a different centre and produced 100% success in metalwork retention. The present study is a reproducibility test of the same technique.MethodsA retrospective review was performed on 24 patients with infected orthopaedic metalwork, including 3 upper limb and 21 lower limb cases, for outcomes relating to implant retention and infection resolution. Patients underwent a modified NPWT technique as an adjunct to antibiotic therapy and surgical debridement. Detailed medical and microbiology information were obtained from the patient records.Results23 of 24 (96%) patients had successful metalwork retainment with healed wounds and resolution of infection, allowing fracture union. 27 infective organisms were identified in this cohort, and the antibiotic regimens for each patient are provided. The average follow-up was 663 days. No adverse effects were observed.ConclusionThis series supports the modified NPWT technique as a safe, reliable and effective adjunct therapy to resolve metalwork infection. The same results have been reproduced as the previous cohort in a different centre.

Stellate Ganglion Phototherapy Using Low-Level Laser

This study investigates the effect of stellate ganglion (SG) phototherapy in healthy participants and assesses its efficacy in suppressing electrical storm (ES) refractory to antiarrhythmic drugs and catheter ablation.Modulation of the autonomic nervous system has been shown to be an effective adjunctive therapy for ES.Ten-minute SG phototherapy was performed twice weekly for 4 weeks in 20 healthy volunteers. To evaluate the acute and chronic effects of SG phototherapy, heart rate variability and serum concentrations of adrenaline, noradrenaline, and dopamine were obtained before phototherapy, immediately after the first phototherapy session, after 8 sessions of phototherapy, and 3 months after the first phototherapy session. In addition, the efficacy of SG phototherapy was evaluated in 11 patients with ES refractory to medication, sedation, and catheter ablation.In healthy participants, serum adrenaline concentration significantly decreased after phototherapy, whereas low-frequency power/high-frequency power significantly decreased during phototherapy. Moreover, the effect on heart rate variability did not last beyond 3 months. In the clinical pilot study, 7 patients had a suppression of ES after SG phototherapy; however, without maintenance therapy, 2 patients had a recurrence of ventricular arrhythmias. Furthermore, it did not control ES in 4 patients.SG phototherapy reduced sympathetic activity and may be a safe and effective adjunctive therapy to control ES in some patients, but its long-term efficacy remains unknown. Chronic phototherapy might help reduce ES recurrence.

Acupuncture as an adjunctive therapy for arrhythmia: a Delphi expert consensus survey.

Current evidence suggests that acupuncture is an effective adjunctive therapy that can bring potential benefits to patients with cardiac arrhythmias. However, there are relevant gaps in the optimal therapeutic strategy, which may cause uncertainties on the best practice of acupuncture treatment for arrhythmia. We aim to develop consensus-based recommendations for clinical guidance on acupuncture treatment of cardiac arrhythmias. A multidisciplinary panel of specialists was invited to participate in a two-round semi-open clinical issue investigation. Meanwhile, relevant literature reviews were searched in 3 databases to provide evidence. Subsequently, an initial consensus voting list on acupuncture as an adjunctive therapy for cardiac arrhythmias was derived from the clinical investigation and literature review. Finally, 30 authoritative experts reached a consensus on the key issues of the voting list by a three-round modified Delphi survey. Consensus was defined when >80% agreement was achieved. Following the three-round Delphi survey, there were 32 items (91.43%) finally reaching consensus, including the following 5 domains: (I) the benefits of acupuncture for the appropriate population; (II) the general therapeutic principle; (III) the acupuncture strategy; (IV) the relevant adverse events; (V) others. Consensus was achieved on some key elements. Given the lack of guidelines and the substantial heterogeneity of previous studies, these recommendations are of value in providing guidance for clinical practice of acupuncturists and in assisting patients with arrhythmia to obtain standardized acupuncture treatment. It also pointed out some problems that need to be carefully explored in future studies.

Ketogenic diets in the management of type 1 diabetes: Safe or safety concern?

The jury is still out on whether a low-carbohydrate, ketosis-inducing diet is an effective and safe adjunctive therapy to insulin in type 1 diabetes. The limited published literature reports an association with weight loss and improved glycemic control and may, over the long-term, lead to reduced macrovascular and microvascular harm. However, the attendant increased risk of dyslipidemia, diabetic ketoacidosis, and hypoglycemia warrant caution, close monitoring of patients who embark on the diet, and further research.

Hyperbaric Oxygen Therapy Is an Effective Adjunctive Therapy to Manage Treatment-Resistant Venous Leg Ulcers.

We report five cases of venous leg ulcers (VLU) that were resistant to conservative therapy for 22–119 months and were eventually healed via hyperbaric oxygen therapy (HBOT). In one patient, VLU recurred four times and was managed using HBOT, each time. The VLU sizes ranged from 18 to 68 cm2 before HBOT. HBOT was administered at 2.0 atmospheres absolute with 100% oxygen for 60 min per session, five sessions a week during hospitalization. All VLUs healed after 17–66 sessions of HBOT.

Double-blind, randomized, placebo-controlled pilot study of the phosphodiesterase-3 inhibitor cilostazol as an adjunctive to antidepressants in patients with major depressive disorder.

AimsCilostazol (CLS) has shown antidepressant effect in cardiovascular patients, post‐stroke depression, and animal models through its neurotrophic and antiinflammatory activities. Consequently, we aimed to investigate its safety and efficacy in patients with MDD by conducting double‐blind, randomized, placebo‐controlled pilot study.Methods80 participants with MDD (DSM‐IV criteria) and Hamilton Depression Rating Scale (HDRS) score >20 were treated with CLS 50 mg or placebo twice daily plus escitalopram (ESC) 20 mg once daily for six weeks. Patients were evaluated by HDRS scores (weeks 0, 2, 4, and 6). Serum levels of CREB1, BDNF, 5‐HT, TNF–α, NF‐ κB, and FAM19A5 were assessed pre‐ and post‐treatment.ResultsCo‐administration of CLS had markedly decreased HDRS score at all‐time points compared to the placebo group (p < 0.001). Early improvement, response, and remission rates after 6 weeks were significantly higher in the CLS group (90%, 90%, 80%, respectively) than in the placebo group (25%, 65%, 50% respectively) (p < 0.001). Moreover, the CLS group was superior to the placebo group in modulation of the measured neurotrophic and inflammatory biomarkers.ConclusionCLS is safe and effective short‐term adjunctive therapy in patients with MDD with no other comorbid conditions.Trial registration ID:NCT04069819.

Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis

Neovascular age-related macular degeneration (nAMD) commonly causes vision loss from aberrant angiogenesis, termed choroidal neovascularization (CNV). Interleukin-6 (IL6) is a pro-inflammatory and pro-angiogenic cytokine that is correlated with AMD progression and nAMD activity. We hypothesize that anti-IL6 therapy is a potential nAMD therapeutic. We found that IL6 levels were increased after laser injury and expressed by macrophages. Il6-deficiency decreased laser-induced CNV area and exogenous IL6 addition increased choroidal sprouting angiogenesis. Il6-null mice demonstrated equally increased macrophage numbers as wildtype mice. At steady state, IL6R expression was detected on peripheral blood and ocular monocytes. After laser injury, the number of IL6R+Ly6C+ monocytes in blood and IL6R+ macrophages in the eye were increased. In human choroid, macrophages expressed IL6, IL6R, and IL6ST. Furthermore, IL6R+ macrophages displayed a transcriptional profile consistent with STAT3 (signal transducer and activator of transcription 3) activation and angiogenesis. Our data show that IL6 is both necessary and sufficient for choroidal angiogenesis. Macrophage-derived IL6 may stimulate choroidal angiogenesis via classical activation of IL6R+ macrophages, which then stimulate angiogenesis. Targeting IL6 or the IL6R could be an effective adjunctive therapy for treatment-resistant nAMD patients.

Psycho-physio-biochemical modulations brought by Integrated Amrita Meditation (IAM®) relieved stress and improved glycemic control in type 2 diabetic subjects

Background and objectivesIn type 2 diabetic subjects, psychological stress worsens glycemic regulation. This study put forward the various psychophysiological and biochemical benefits of the Integrated Amrita Meditation (IAM®) technique in type 2 diabetic subjects in achieving a better quality of life MethodsThis was a clinical trial conducted in the Endocrinology department of Amrita Institute of Medical Sciences. 85 type 2 diabetic subjects between the age group of 30–65 years were recruited for the study. They were randomly allocated to IAM (n = 43) and the control group (n = 42). All the physiological, biochemical, and psychological variables were assessed at baseline, 3 months, and 6 months ResultsWithin the experimental group there was statistically significant reduction in heart rate, respiratory rate, blood pressure, fasting blood glucose, HbA1c, insulin and insulin resistance (p < 0.05). The average percentage changes of these variables between the groups were also significant. HDL showed an increase within the IAM®group (p < 0.001) while there was an increase in LDL and total cholesterol in the control group. Between the groups, the mean percentage changes in stress hormones cortisol and adrenaline were also significant. IgA (p = 0.002) and GABA (p = 0.007) significantly increased in the experimental group. Psychological stress assessed by perceived stress scale also showed a significant drop after the intervention in the test group and the change in perceived stress was again significant between the 2 groups comparison ConclusionAlong with the standard treatment regimens, diabetic patients can incorporate mind-body relaxation techniques as an effective adjunctive therapy

Extracorporeal Shockwave Therapy for Chronic Venous Ulcers: A Randomized Controlled Trial

Background: Chronic venous ulcers (CVUs), demanding specialized care, are still a major socioeconomic problem facing health care systems worldwide. This study’s main goal was evaluating the efficacy of ESWT application as an AT in the treatment of wounds for curing CVUs. Materials and Methods: 50 patients presenting with CVUs were divided into two groups of ESWT and control randomly. Then, ESWT was applied one session per week, during four weeks, along with routine CB. The control group also received sham ESWT together with CB. In this respect, pain score, wound size, patient satisfaction and quality of life (QoL) using the Charing Cross Venous Ulcer Questionnaire (CCVUQ) were consequently assessed at baseline, week four, and week eight and then compared between both groups. Results: The findings showed that patients receiving ESWT along with CB had significantly lower pain and were also feeling more satisfied than the cases undergoing CB alone (P&lt;0.05). The significant efficiency of ESWT in improving the healing process of CVUs was further observed (P&lt;0.05). In addition, QoL, assessed by the CCVUQ, was significantly higher in patients receiving ESWT (P&lt;0.05). Conclusion: These findings established that ESWT was a feasible and safe option to treat patients presenting with CVUs in another word, ESWT seems to be a safe and effective adjunct therapy (AT) compared with CB in patients with CVUs. [GMJ.2021;10:e1931]

Extracorporeal Shockwave Therapy for Chronic Venous Ulcers: A Randomized Controlled Trial.

Background: Chronic venous ulcers (CVUs), demanding specialized care, are still a major socioeconomic problem facing health care systems worldwide. This study’s main goal was evaluating the efficacy of ESWT application as an AT in the treatment of wounds for curing CVUs.Materials and Methods: 50 patients presenting with CVUs were divided into two groups of ESWT and control randomly. Then, ESWT was applied one session per week, during four weeks, along with routine CB. The control group also received sham ESWT together with CB. In this respect, pain score, wound size, patient satisfaction and quality of life (QoL) using the Charing Cross Venous Ulcer Questionnaire (CCVUQ) were consequently assessed at baseline, week four, and week eight and then compared between both groups.Results: The findings showed that patients receiving ESWT along with CB had significantly lower pain and were also feeling more satisfied than the cases undergoing CB alone (P<0.05). The significant efficiency of ESWT in improving the healing process of CVUs was further observed (P<0.05). In addition, QoL, assessed by the CCVUQ, was significantly higher in patients receiving ESWT (P<0.05). Conclusion: These findings established that ESWT was a feasible and safe option to treat patients presenting with CVUs in another word,ESWT seems to be a safe and effective adjunct therapy (AT) compared with CB in patients with CVUs.

Adjunctive Green Thermal Laser Photocoagulation for Treatment of Resistant Infectious Keratitis.

PurposeTo investigate the safety and efficacy of green thermal laser as an adjunctive therapy for the treatment of resistant infectious keratitis (IK) in the Delta region of Egypt.MethodsA retrospective case series of 150 patients, within a 4 year duration, with resistant IK, who failed to respond to specific medical treatment alone for 7 days, were included. They all received green thermal laser photocoagulation treatment to the cornea as an adjunctive to medical treatment.ResultsForty-eight women and 102 men were included in this study with a mean age of 46.2 ± 7.7 years. Common risk factors associated with IK included trauma by material of plant origin and contact lens wear. The mean duration of healing was 2.87 ± 0.7 weeks. A single session of green thermal laser application was adequate in 138 IK cases (92%), while 12 cases (8%) required an additional session a week later. Supplementary amniotic membrane transplantation (AMT) was required in 26 cases (17.3%). Two patients (1.3%) required tectonic keratoplasty for corneal perforation. The final corrected distance visual acuity (CDVA) was counting fingers (CF) or better in 78 patients (52%). No decrease of CDVA was reported throughout the study.ConclusionGreen thermal laser is a safe and effective adjunctive therapy for the treatment of resistant infectious keratitis.

Efflux pumps in Mycobacterium tuberculosis and their inhibition to tackle antimicrobial resistance.

Tuberculosis (TB), an infectious disease caused by the bacterium Mycobacterium tuberculosis, was the leading cause of mortality worldwide in 2019 due to a single infectious agent. The growing threat of strains of M. tuberculosis untreatable by modern antibiotic regimens only exacerbates this problem. In response to this continued public health emergency, research into methods of potentiating currently approved antimicrobial agents against resistant strains of M. tuberculosis is an urgent priority, and a key strategy in this regard is the design of mycobacterial efflux pump inhibitors (EPIs). This review summarises the current state of knowledge surrounding drug-related efflux pumps in M. tuberculosis and presents recent updates within the field of mycobacterial EPIs with a view to aiding the design of an effective adjunct therapy to overcome efflux-mediated resistance in TB.

Nutritional Effects of the Enteral Nutritional Formula on Regulation of Gut Microbiota and Metabolic Level in Type 2 Diabetes Mellitus Mice.

PurposeDue to the adverse effects of antidiabetic drugs, nowadays, nutraceuticals have been of much interest to investigators. Therefore, the present study aimed to explore the potential effects of enteral nutritional (EN) formulas on the gut microbiota and metabolic regulation of type 2 diabetes mellitus (T2DM) mice and compare the differences between whey protein and soy protein.MethodsEN formulas made of whey protein or soy protein were administered for five weeks and then mice tissue samples were obtained to examine the metabolic parameters and histopathology of the pancreas, liver, jejunum and colon. 16S rRNA V3-V4 region gene sequencing was used to analyze the changes in the gut microbiota.ResultsAfter the five-week intervention, the alpha diversity had recovered slightly, and the soy protein group (SPG) achieved a better effect than the whey protein group (LPG). The overall composition of gut microbiota was regulated. The abundance of Bacteroidetes and TM7 had raised significantly and the abundance of Firmicutes and Deferribacteres had declined after treatment, with no significant difference between the LPG and SPG. The types of beneficial bacteria were increased at the genus and species level. The level of hexokinase (HK) and pyruvate kinase (PK) had significantly recovered and inhibited the level of α-glucosidase. In addition, the EN formulas treatment reduced the levels of inflammatory factor (TNF-α) in liver and muscle. The level of glucose transporter type 2 (GLUT-2) levels in the liver and intestine also significantly increased. Moreover, the metabolism regulation of the SPG was better than that of the LPG. The EN formulas treatment improved the pancreas, liver, jejunum and colon histology.ConclusionThe EN formulas regulated the overall structure of the gut microbiota and improved the metabolic level in streptozotocin/high-fat diet (STZ/HFD) diabetic mice. Therefore, EN formula may potentially become an effective nutritional adjunctive therapy for T2DM.