Different studies described the antibacterial properties of Lavandula angustifolia (Mill.) essential oil and its anti-inflammatory effects. Besides, no data exist on its ability to activate human macrophages during the innate response against Staphylococcus aureus. The discovery of promising regulators of macrophage-mediated inflammatory response, without side effects, could be useful for the prevention of, or as therapeutic remedy for, various inflammation-mediated diseases. This study investigated, by transcriptional analysis, how a L. angustifolia essential oil treatment influences the macrophage response to Staphylococcus aureus infection. The results showed that the treatment increases the phagocytic rate and stimulates the containment of intracellular bacterial replication by macrophages. Our data showed that this stimulation is coupled with expression of genes involved in reactive oxygen species production (i.e., CYBB and NCF4). Moreover, the essential oil treatment balanced the inflammatory signaling induced by S. aureus by repressing the principal pro-inflammatory cytokines and their receptors and inducing the heme oxygenase-1 gene transcription. These data showed that the L. angustifolia essential oil can stimulate the human innate macrophage response to a bacterium which is responsible for one of the most important nosocomial infection and might suggest the potential development of this plant extract as an anti-inflammatory and immune regulatory coadjutant drug. Abbreviations: CE: controlled environment; EO: essential oil; LA: Lavandula angustifolia Mill.; MDM: monocyte-derived macrophages; NE: natural environment; Neg-Res: negative responsive donors; TLR-IL1R: Toll-like receptor-interleukin 1 receptor; Pos-Res: positive responsive donor

Given the known pro-oxidant status of tumour cells, the development of anti-proliferative strategies focuses on products with both anti- and pro-oxidant properties that can enhance antitumour drug cytotoxicity. We used a C. zeylanicum essential oil (CINN-EO) and assessed its effect on a human metastatic melanoma cell line (M14). Human PBMCs and MDMs from healthy donors were used as normal control cells. CINN-EO induced cell growth inhibition, cell cycle perturbation, ROS and Fe(II) increases, and mitochondrial membrane depolarization. To assess whether CINN-EO could affect the stress response, we analysed iron metabolism and stress response gene expression. CINN-EO increased HMOX1, FTH1, SLC7A11, DGKK, and GSR expression but repressed OXR1, SOD3, Tf, and TfR1 expression. HMOX1, Fe(II), and ROS increases are associated with ferroptosis, which can be reversed by SnPPIX, an HMOX1 inhibitor. Indeed, our data demonstrated that SnPPIX significantly attenuated the inhibition of cell proliferation, suggesting that the inhibition of cell proliferation induced by CINN-EO could be related to ferroptosis. Concurrent treatment with CINN-EO enhanced the anti-melanoma effect of two conventional antineoplastic drugs: the mitochondria-targeting tamoxifen and the anti-BRAF dabrafenib. We demonstrate that CINN-EO-mediated induction of an incomplete stress response specifically in cancer cells affects the proliferation of melanoma cells and can enhance drug cytotoxicity.

(1) Introduction: Bacterial resistance to antibiotics is estimated to be the cause of a major number of deaths by 2050 if we do not find strategies to slow down the rise of drug resistance. Reviews on Mediterranean wild edible plants (MWEPs) with antimicrobial properties are scarce in the main databases (PubMed, Scopus, and WoS). Hence, we proceeded to conduct a new review of the studies on MWEPs. (2) Methods: We used ‘wild edible plant’ and ‘antimicrobial’ as keywords. Within this group, exclusion criteria were reviews, studies concerning non-Mediterranean plants or non-edible plants, studies on topics other than plants or containing no description of antimicrobial properties, or off-topic studies. (3) Results: Finally, out of the one hundred and ninety-two studies we had started with, we reviewed thirty-eight (19.8%) studies concerning the antimicrobial properties of seventy-four MWEPs species belonging to twenty-five Families. Fifty-seven (77%) species out of seventy-four proved to be antimicrobial, with a stringent threshold selection. (4) Conclusions: Studies are still very heterogeneous. We still know too little about MWEPs’ properties; however, what we already know strongly recommends carrying on investigation.

Increased HIV drug resistance (HIVDR) with antiretroviral therapy (ART) rollout may jeopardize therapeutic options, especially in this era of transition to fixed-dose tenofovir-lamivudine-dolutegravir (TLD). We studied acquired HIVDR (ADR) patterns and describe potentially active drugs after first- and second-line failure in resource-limited settings (RLS) like Cameroon. A laboratory-based study with 759 patients (≥15 years) experiencing virological failure was carried out at the Chantal Biya International Reference Centre (CIRCB), Yaoundé, Cameroon. Socio-demographic, therapeutic and immunovirological data from patient records were analysed according to HIV-1 genotypic profiles. Median (IQR) ART-duration was 63 (50–308) months. Median CD4 and viremia were 153 (IQR:50–308) cells/mm³ and 138,666 (IQR:28,979–533,066) copies/mL, respectively. Overall ADR was high (93.4% first-line; 92.9%-second-line). TDF, potentially active in 35.7% of participants after first-line and 45.1% after second-line, suggested sub-optimal TLD-efficacy in second-line (64.3%) and third-line (54.9%). All PI/r preserved high efficacy after first-line failure while only DRV/r preserved high-level efficacy (87.9%) after second-line failure. In this resource-limited setting (RLS), ADR is high in ART-failing patients. PI/r strategies remain potent backbones for second-line ART, while only DRV/r remains very potent despite second-line failure. Though TLD use would be preferable, blind use for second- and third-line regimens may be sub-optimal (functional monotherapy with dolutegravir) with high risk of further failure, thus suggesting strategies for selective ART switch to TLD in failing patients in RLS.

Achieving and maintaining viral suppression (VS) in pediatric populations remain suboptimal in low- and middle-income countries (LMICs), calling for the optimized management approaches. We compared the rate of confirmed virological failure (cVF) and associated factors among virally non-suppressed (VnS) children and adolescents after enhanced adherence counseling (EAC) on dolutegravir-based versus other regimens. A multicentre and prospective cohort study was conducted among ART-experienced children (<10 years) and adolescents (10–19 years) with VnS followed-up for confirmatory viral load (VL) after EAC. cVF was defined as 2 consecutive VL ≥ 1000 copies/mL after ≥6 months of ART and EAC. Overall, 250 individuals with VnS were enrolled, median [IQR] age was 12 (11–13) and median duration on ART was 57 (48–67) months. According to ART-regimens, 48.4% received DTG-based regimens (TDF/3TC/DTG: 32.8%; ABC/3TC + DTG: 15.6%). Overall, cVF rate was 39.2% (95% CI: 33.3–45.3), with a longer duration on ART among cVF-group (68 [60–79] months) versus VS-group (48 [45–61]), P = .026. According to ART-regimen, cVF rate was 29.3% in those receiving TDF/3TC/DTG versus 43.5% for ABC/3TC + ATV/r/LPV/r and 25.6% for ABC/3TC + DTG, P = .007. Regarding anchor-drugs, cVF with DTG, EFV and ATV/r/LPV/r was 28.1%, 48.4% and 49.2%, respectively, P = .007. Interestingly, 13.2% of participants with VS had detectable low-level viremia (400–999 copies/mL), with 5.8%, 7.7% and 12.9% being observed in those receiving DTG, ATV/r/LPV/r, and EFV/NVP-based regimen, respectively, P = .013. Only anchor-drug was found to be a predictor of cVF. Compared to those receiving DTG-based regimens, ART based on ATV/LPV/r (aOR [95% CI]: 0.298 [0.132–0.72], P = .004) or EFV/NVP (aOR [95% CI]: 0.401 [0.163–0.983], P = .046) was significantly less likely to achieve VS. About 40% of Cameroonian children/adolescents with VnS experience cVF, which is indicative that EAC significantly contributes to viral re-suppression (60%), especially with DTG-based regimens. Thus, implementing a strategy that couples DTG-transition with EAC-interventions would contribute substantially to efforts in eliminating pediatric AIDS in LMICs.

Dual therapies (DT) combining integrase strand transfer inhibitors (INSTIs) with second-generation non-nucleoside reverse transcriptase inhibitors (2nd-Gen-NNRTIs) offer new possibilities for HIV treatment to improve adherence. However, drug resistance associated mutations (RAMs) to prior antiretrovirals may jeopardize the efficacy of DT. We herein describe the predicted efficacy of DT combining INSTIs + 2nd-Gen-NNRTI following treatment failure among Cameroonian patients. We genotyped the HIV-1 pol gene using Sanger sequencing and assessed acquired RAMs to NNRTIs and INSTIs in patients failing treatment from March 2019 to December 2023. Drug susceptibility was interpreted using Stanford HIVdb v9.5, and statistical analyses were performed using SPSS v22. Of 130 successfully genotyped participants (median age (IQR): 38 (27–46) years; 59.2% female), 92.3% had RAMs to NNRTIs and 1.5% to INSTIs. Prevailing RAMs were Y181C (32.3%) among NNRTIs and R263K (0.7%) among INSTIs. Among 2nd-Gen-NNRTIs, etravirine, doravirine and rilpivirine had 43.85%, 41.54% and 38.46% genotypic sensitivity, respectively. Among INSTIs, we found 97.69% efficacy for dolutegravir/bictegravir, 96.15% for cabotegravir and 92.31% for elvitegravir/raltegravir. The overall predictive efficacy of DT was lower among participants who failed 1st-Gen-NNRTI (p < 0.001); with etravirine + dolutegravir/bictegravir combination showing the highest score (43.8%). Conclusively, DT combining INSTIs + 2nd-Gen-NNRTIs might be suboptimal in the context of previous ART failure, especially with NNRTI-based treatment in low- and middle-income countries. The general data clearly indicate that without resistance testing, it is nearly impossible to use long-acting dual therapies in previously failing patients.