D1 D3 Research Articles

Morphological, phylogenetic, and biogeographical characterization of Ostreopsis fattorussoi (Dinophyceae) from the Gulf of Aden, Western Indian Ocean, Djibouti

ABSTRACT Research on toxic dinoflagellates is virtually non-existent in the region extending from the Gulf of Aden to the coast of the Republic of Djibouti, despite reports of red tides since 1998 in the Gulf of Tadjoura, which have a significant impact on marine life. In this context, a programme to explore the diversity of potentially toxic dinoflagellates was initiated in 2022/2023 in the Gulf of Tadjoura. During this initiative, six strains of the genus Ostreopsis were established from macroalgae samples, primarily Sargassum binderi. Detailed morphological and molecular analyses (light microscopy, SEM, and various genetic markers such as the ITS region and the D1–D3 and D8–D10 regions of LSU rDNA) confirmed that the six isolates were epibenthic dinoflagellates belonging to the species Ostreopsis fattorussoi. This study represents the first report of O. fattorussoi in the Gulf of Aden and the first morpho-molecular identification of this species outside the North Atlantic and Mediterranean regions. The identification of this species opens new essential research avenues for exploring its ecology and toxicology. More broadly, this work enriches the knowledge of microalgae and emphasizes the crucial importance of establishing monitoring systems for algal blooms, given their impacts on the environment, public health, as well as the fishing and tourism sectors, which can suffer significant economic losses.

Structural Characterization of the Pan-African Banyo Area (Western Cameroon Domain): Constraints from Field Observations, Structures and AMS

The Banyo area, located in the southern prolongation of the Mayo Nolti shear zone trend, belongs to the western Cameroon domain of the Neoproterozoic Central African Belt (NCAB). It is made of granitic rocks that intrude metamorphic banded rocks. Both are sometimes mylonitized. The pluton is dominantly of paramagnetic behavior, as shown by the hysteresis loops and the Fe-bearing silicates crystals are the susceptibility carriers. AMS ellipsoids are dominantly of oblate shape, pointing to the importance of flattening during pluton emplacement. The anisotropy degree of magnetic susceptibility values (≤1.20) characterize the magmatic fabric flow. The microstructural study of the granite reveals magmatic, sub-magmatic, solid-state and mylonitic deformations. Field and AMS fabrics show evidence of polyphase deformation (D1–D3). The D1 phase is of flattening mechanism (flat-laying foliation). The D2 phase points to sinistral ductile simple shear accommodating moderate to steep dipping and N-S- to NW-SE-oriented foliations in plutonic and country rocks and conjugated E-W mylonitic foliation in country rocks bearing sub-horizontal- to moderate-plunge mineral stretching lineation. The D3 phase is of dextral ductile simple shear. σ- and δ-type kinematic markers in the pluton indicate sinistral top-to-south sense of shear movement, indicating a non-coaxial component of the tectonics. The magnetic fabrics of the pluton are parallel to those of the D2 deformation phase of the study area. The transpressive D2 and D3 events correlate with the D2 and D3 phases of the Pan-African tectonic dated at 613–585 Ma and 585–540 Ma, respectively. The pluton, then, emplaced during regional sinistral D2 deformation under transpressive regime. The emplacement of the NE Banyo granite took place as rock strips sheared in sinistral sense of shear movement.

Design, synthesis and antioxidant, anticancer and antimicrobial activity evaluation of novel resveratrol derivatives

Resveratrol, a stilbene in soybeans, grapes, pines, legumes, pomegranates, and peanuts, exhibits varied bioactivity. It is antioxidant, provides photoprotection, demonstrates anti-inflammatory, antipyretic, cardioprotective, antiestrogenic, anticancer, and antimicrobial effects, while also inhibit platelet aggregation. This study reports design, synthesis, and biological activity of its 3 (d1–d3) new diazo derivatives using bioisoster strategy. In DPPH test, d1 showed excellent antioxidant activity (IC50 = 19.95 µg/mL), close to resveratrol (IC50 = 21.23 µg/mL). Anticancer properties, estimated by brine shrimp lethality test (BSLT), showed appreciable LC50 value of 70.4 μg/mL for d3, again near to resveratrol (LC50 = 73.4 μg/mL). In MTT cytotoxicity test, d2 recorded LC50 value of 30.7 μg/mL, considerably better than resveratrol (LC50 = 72.3 µg/mL). In antimicrobial tests, d3 appeared very effective against eight bacterial and two fungal pathogenic strains. These findings candidate the derivatives as suitable ingredients for application in pharmaceutical and/or food industries after necessary supplementary studies.

Rapeseed and Palm Oils Can Improve the Growth, Muscle Texture, Fatty Acids and Volatiles of Marine Teleost Golden Pompano Fed Low Fish Oil Diets

This study evaluated the effects of different lipid sources—fish oil (FO), soybean oil, rapeseed oil, and palm oil—on the growth and muscle quality of golden pompano (Trachinotus ovatus) cultured in offshore cages for 10 weeks. Three diets (D1–D3) were formulated: D1 used only fish oil, D2 blended fish, rapeseed oil, and palm oil, and D3 combined fish and soybean oils. Fish in the D1 group showed the highest weight gain, specific growth rate, and muscle protein content, significantly outperforming D3. No significant differences in muscle lipid content or edible quality were found between groups. D1 had the highest levels of long-chain and n-3 polyunsaturated fatty acids (PUFA), while D3 had higher n-6 PUFA. Saturated and monounsaturated fatty acids were higher in D1 and D2 than in D3. Muscle volatiles like aldehydes and amines were elevated in D1, with more pleasant flavors compared to D2 and D3. Muscle texture was superior in D2. These results suggest that rapeseed and palm oils can enhance growth, flavor, and texture in fish on low FO diets, offering a sustainable alternative to reduce reliance on marine-based feed in aquaculture.

First observation of a Pyrodinium bahamense bloom in the Gulf of Aden, Djibouti: morpho-molecular characterization and spatio-temporal abundance

ABSTRACT At the end of the summer of 2023, in September, an intense water discolouration (red tide) accompanied by fish mortality was observed in the Gulf of Tadjoura. This discolouration of the seawater was caused by a potentially toxic dinoflagellate, Pyrodinium bahamense. The proliferation, located near the coast between the Moucha/Maskali islands and the city of Tadjoura, was significant enough to be detected by satellite imagery. P. bahamense had formed an almost monospecific bloom (90%), with a density of 1.8 × 106 cells l‒1 (22 September 2023). Other dinoflagellates such as Dinophysis miles, Dinophysis caudata, Tripos furca, Lingulaulax sp. (formerly Lingulodinium), Balechina sp. and Protoperidinium sp. were detected at very low concentrations. This study characterizes P. bahamense through an integrated approach, combining detailed morphological analysis with molecular phylogenetic analyses based on the internal transcribed spacer (ITS) region and the D1–D3 regions of large subunit ribosomal (LSU rDNA). For the first time, we have molecularly identified the toxic ribotype from the Indo-Pacific in the Gulf of Aden region. This discovery highlights an emerging risk of this toxic ribotype in the eastern Mediterranean basin. This region, already facing various environmental challenges, may see its vulnerability heightened with the emergence of new risks.

Alendronate sodium induces G1 phase arrest and apoptosis in human umbilical vein endothelial cells by inhibiting ROS-mediated ERK1/2 signaling

Alendronate sodium induces G1 phase arrest and apoptosis in human umbilical vein endothelial cells by inhibiting ROS-mediated ERK1/2 signaling

Morphometrics of IPB D1, IPB D2 and IPB D3 Chickens Aged 4 to 12 Weeks at Sinar Harapan Farm Sukabumi

Research on the 11 morphometrics of IPB-D chicken in Sukabumi district has not been conducted. This study aimed to evaluate the morphometrics of IPB D1, IPB D2 and IPB D3 chickens in Sukabumi District. The design of this study was a completely randomized design with 3 levels of treatment linesnamely IPB D1, IPB D2 and IPB D3 with 95% confidence interval. Treatments that had a significant effect were followed by the Tukey test. Measured morphometric parameters such as shank length, shank circumference, femur length, tibia length, breast length, breast width, breast depth, breast circumference and back length. IPB D3 chickens show that their genetic condition is not yet stable as meat type. At the age of 4 to 8 weeks, IPB-D3 chickens have a larger size in the variables of shank circumference, femur length, tibia length, breast length and breast circumference. However, at the age of 8 to 12 weeks IPB-D3 chickens have a smaller size in the variables of breast length, breast width, breast depth, breast circumference and back length. Meanwhile, IPB D1 chickens show that they are genetically stable and IPB D2 is able to adapt because of its resistance traits.

Reactive Dyes Bearing Bis(Monochlorotriazine) Group: Synthesis, Photophysical Properties and Realization of Salt‐Free Dyeing

AbstractA series of novel reactive dyes D1–D3 based on vinamidinium salt were designed and synthesized. Bis(monochlorotriazine) was introduced as the reactive group and sodium sulfonate was the water‐soluble group. Their photophysical properties were studied systematacially. The strong and sharp ground‐state absorption peak in the 250–320 nm range in the UV‐vis absorption spectrum of the aqueous solution could be attributed to the 1π–π* transition by the parent structure of the dyes, and the relatively broad absorption peak in the range of 300–650 nm could be attributed to the 1π–π* mixed intramolecular charge transfer. By applying this series of reactive dyes to the dyeing of four fabrics (silk, cotton, polyester/cotton blends, and polyester), the dyeing depths were in the range of 5.2–28.6 under salt‐free conditions. The results show that D3 with higher planarity can increase the dyeing depth. At length, fastening tests on dyed cotton fabrics and silk showed that this series of reactive dyes had a color fastness between grades 3 and 5 for abrasion and soap‐washing. In summary, these reactive dyes could be potential dyes for salt‐free dyeing applications.

Essential role of Moringa-albumin (MA) formulation in the maintenance of complement regulatory proteins on erythrocyte (TER-119) cells in diabetic mouse models.

To evaluate the essential role of Moringa-albumin (MA) formulation in the maintenance of complement regulatory proteins through CD55 and CD59 on erythrocyte (TER-119). Streptozotocin (145 mg/kg) was used to induce diabetes mice. In diabetes mellitus (DM) model mice were treated with MA formulation for 14 days at a D1 - 500 mg/kg (M) + 620 mg/kg BW (A), D2 - 1000 mg/kg (M) + 420 mg/kg (A), and D3 - 1500 mg/kg (M) + 200 mg/kg (A). On the 15th day, the mice were dissected for the isolation of their bone marrow by the flushing method. The analysis flow cytometry was performed to find out the TER-119, CD55, and CD59 expressions. The data were statistically analysed with one-way ANOVA (ρ≤ 0.05) and Tukey test using SPSS version 16 for Windows. The effect of MA administration in D3 group have a significant effect on increasing the profile of erythrocytes (TER-119), compared to DM (ρ≤0.05) group (STZ Injection-no treatment), as well as CD59 expressed by erythrocytes. MA administration in D1 group and D3 group significantly increased the profile of CD55 expressed by erythrocytes compared to DM (ρ≤0.05). MA formulation with D3 group (1500 mg/kg (M) + 200 mg/kg (A)) was able to maintain or control complement regulatory proteins (CD55 and CD59) on red blood cells (erythrocytes/TER-119) in DM.

Redescription of Dracovermis occidentalis (Digenea: Liolopidae) infecting American alligator, Alligator mississippiensis from the Bon-Secour River (Mobile–Tensaw River Delta, Alabama, USA) and a revised phylogeny for Liolopidae

We examined several American alligators, Alligator mississippiensis (Daudin, 1802) (Crocodilia: Alligatoridae) from Louisiana, Alabama, and South Carolina in August 2022. The intestine of one alligator from Alabama was infected by Dracovermis occidentalis Brooks and Overstreet, 1978 (Platyhelminthes: Digenea: Liolopidae Odhner, 1912), a seldom collected and incompletely described trematode that lacks a representative nucleotide sequence. Liolopidae comprises 5 genera and 15 species: Liolope spp. infect giant salamanders; Helicotrema spp. infect turtles and lizards; Harmotrema spp. infect snakes; Paraharmotrema spp. infect turtles; and Dracovermis spp. infect crocodilians. Based on our study of the newly collected specimens and the holotype of D. occidentalis, we redescribe D. occidentalis, correct errors in its original description, and provide an updated phylogeny for Liolopidae that, for the first time, includes Dracovermis Brooks and Overstreet, 1978. Our specimens were identified as D. occidentalis by having testes in the posterior 1/3 of the body, a pretesticular cirrus sac, a spined and eversible cirrus, a bipartite seminal vesicle, and a post-acetabular vitellarium. A phylogenetic analysis of the D1–D3 domains of the nuclear large subunit ribosomal DNA (28S) recovered Liolopidae as monophyletic; however, low taxon sampling in the group precludes hypothesis-testing about liolopid-vertebrate cophyly. This is the first collection for morphological study of the type species for Dracovermis since the genus was proposed 46 years ago, the first record of a liolopid from Alabama, and the first phylogenetic analysis that includes Dracovermis.

Efecto de la densidad de población y temperatura en dos periodos de crecimiento de juveniles de chita <i>Anisotremus scapularis</i> (Perciformes: Haemulidae) en sistemas de recirculación en acuicultura

Recirculating aquaculture systems (RAS) are being used to maintain the development stages of the Peruvian grunt Anisotremus scapularis. In this sense, the stocking density and temperature factors were evaluated in two growth periods, as well as their influence on the growth, feeding, survival and well-being of the juveniles, to use the maximum potential of the RAS. Three stocking density (low D1, medium D2 and high D3) and two temperatures (20 ± 1 °C and 24 ± 1 °C) were tested. The experiment was carried out in two periods (6 and 28 g). In each of the treatments, specific growth rate (SGR), thermal growth coefficient (TGC), coefficient of variation (CV), feed conversion rate (FCR), feeding rate (FR), condition factor (K) and survival were calculated. The treatment with the best results in the first period was the density D3 and the temperature of 24 ºC, reaching a final density of 15.6 kg.m-3, SGR: 2% día-1, TGC: 0.5, CV: 15.4%, FCR: 1.2, FR: 2.8% and K: 2. In the second period, the best treatment was the density D3 and the temperature of 20 ºC, reaching a final density of 11.4 kg.m-3, SGR: 1.5% día-1, TGC: 0.2, CV: 15.2, FCR: 2.3, FR: 2.8% and K: 2.3. Survival for all treatments was 100% in both periods. Therefore, the best performance in terms of growth, feeding and well-being of juvenile Peruvian grunt in the two periods of development was obtained at the highest densities (5.3 and 5 kg.m-3) and at a temperature of 24 °C in 6 g juveniles and 20 °C in 28 g juveniles under laboratory conditions.

Saponins from Dolichos lablab seeds with anti-inflammatory activity

Saponins from Dolichos lablab seeds with anti-inflammatory activity

Magnetic and resistivity imaging of a probable fault within the Precambrian crystalline rocks in Ogbomoso, Southwestern Nigeria

A linear structure which is interpreted to be a fault was identified within the Precambrian basement complex rocks of the Ogbomoso Southwest Sheet 222 geological map, southwest Nigeria. The ground magnetic and electrical resistivity methods were used to investigate the structure and determine its physical characteristics. Five (5) traverses with lengths varying from 700–800 m and trending approximately NW–SE were established perpendicularly to the suspected fault. Total magnetic field data were acquired at 10 m interval, corrected for diurnal variation and inverted into 2D magnetic models using the Geosoft Oasis montaj software package. Dipole-Dipole resistivity data were acquired along the traverses using a dipole length of 20 m with expansion factor n varying from 1 to 5 and modelled to generate 2D resistivity structures with the DIPPROTM software package. Thirty-seven (37) depth sounding datasets were acquired, quantitatively interpreted and the results used to generate geoelectric sections across the suspected geologic feature. Three major magnetic dyke lineaments D1, D2 and D3 (60 – 164 m wide and 70 – ∞ depth extent) characterised by peak negative (−44 to −81 nT) magnetic anomalies and equivalent resistivity lineaments R1, R2 and R3 (50 – 140 m wide and 40 to >60 m depth extent) typified by low resistivity (10 – 750 Ωm) vertical discontinuities were delineated. The northern edges of lineaments D2 and R2 coincide significantly with the spatial location of the suspected fault F1 – F1 while D1 and R1 and D3 and R3 correlated and are newly identified parallel faults F2 – F2 and F3 – F3 to F1 – F1 and probably syngenetic with it.

Timing and Tectonic Implications of the Development of the Orosirian Qianlishan Ductile Shear Zones in the Khondalite Belt, North China Craton

Orogen-parallel ductile shear zones are conspicuous structures in the Khondalite Belt, but the timing of shearing remains poorly understood. Here, we present field-based structural and zircon U-Pb geochronological studies on the newly discovered Qianlishan ductile shear zones (QDSZ) in the Khondalite Belt. Our results show that the nearly E-W-trending QDSZ are characterized by steeply S(SW)-dipping mylonitic foliations and mainly display a top-to-N(NE) sense of shearing. Two pre-kinematic intrusions yielded zircon crystallization ages of 2055 ± 17 Ma and 1947 ± 9 Ma, providing the maximum age limit for the QDSZ. Additionally, zircon overgrowth rims from three high-temperature mylonites gave metamorphic ages of 1902 ± 8 Ma, 1902 ± 26 Ma and 1884 ± 12 Ma, interpreted to record the timing of development of the QDSZ. Integrated with previous studies, we propose that the Qianlishan Complex suffered three phases of Orosirian deformation (D1–D3), of which the D3 deformation led to the development of the QDSZ. Deformation events D1, D2 and D3 are considered to have occurred at ca. 1.97–1.93 Ga, 1.93–1.90 Ga and 1.90–1.82 Ga, respectively. These events document that the Khondalite Belt underwent a protracted (>100 Myr) orogenic history in response to the collision between the Yinshan and Ordos blocks.

Kinetics of glucose-6-phosphate dehydrogenase (G6PD) activity during Plasmodium vivax infection: implications for early radical malaria treatment

BackgroundPlasmodium vivax relapses due to dormant liver hypnozoites can be prevented with primaquine. However, the dose must be adjusted in individuals with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. In French Guiana, assessment of G6PD activity is typically delayed until day (D)14 to avoid the risk if misclassification. This study assessed the kinetics of G6PD activity throughout P. vivax infection to inform the timing of treatment.MethodsFor this retrospective monocentric study, data on G6PD activity between D1 and D28 after treatment initiation with chloroquine or artemisinin-based combination therapy were collected for patients followed at Cayenne Hospital, French Guiana, between January 2018 and December 2020. Patients were divided into three groups based on the number of available G6PD activity assessments: (i) at least two measurements during the P. vivax malaria infection; (ii) two measurements: one during the current infection and one previously; (iii) only one measurement during the malaria infection.ResultsIn total, 210 patients were included (80, 20 and 110 in groups 1, 2 and 3, respectively). Data from group 1 showed that G6PD activity remained stable in each patient over time (D1, D3, D7, D14, D21, D28). None of the patients with normal G6PD activity during the initial phase (D1–D3) of the malaria episode (n = 44) was categorized as G6PD-deficient at D14. Patients with G6PD activity < 80% at D1 or D3 showed normal activity at D14. Sex and reticulocyte count were statistically associated with G6PD activity variation. In the whole sample (n = 210), no patient had severe G6PD deficiency (< 10%) and only three between 10 and 30%, giving a G6PD deficiency prevalence of 1.4%. Among the 100 patients from group 1 and 2, 30 patients (26.5%) were lost to follow-up before primaquine initiation.ConclusionsIn patients treated for P. vivax infection, G6PD activity did not vary over time. Therefore, G6PD activity on D1 instead of D14 could be used for primaquine dose-adjustment. This could allow earlier radical treatment with primaquine, that could have a public health impact by decreasing early recurrences and patients lost to follow-up before primaquine initiation. This hypothesis needs to be confirmed in larger prospective studies.

Pore heterogeneity analysis and control mechanisms in Cambrian shale of the Shuijingtuo Formation, Yichang area, China

This study focuses on understanding the fractal characteristics and controlling factors of micropore structures within organic-rich shale of the Cambrian Shuijingtuo Formation in the Yichang area of Hubei Province. Mineralogy, petrology, and organogeochemical characteristics were confirmed through comprehensive testing methods, including whole-rock X-ray diffraction and organic geochemical analyses. Additional experiments included low-temperature carbon dioxide adsorption, low-temperature nitrogen adsorption, and high-pressure mercury injection. Fractal dimensions of micropores, mesopores, and macropores were calculated using the V-S, FHH, and MENGER sponge models, respectively. Results indicate that the Cambrian Shuijingtuo Formation represents a typical deposit from an alkaline water body, resulting in high-calcareous shale. Fractal dimensions were as follows: micropores (D1) ranged from 2.1138 to 2.3475 (average 2.2342), mesopores (D2) ranged from 2.5327 to 2.7162 (average 2.6171), and macropores (D3) ranged from 2.7361 to 2.9316 (average 2.82905). Correlations were observed between total organic carbon (TOC) content and Ro with D1 and D2 (positive) and D3 (negative). Shale pore volume and specific surface area exhibited positive correlations with D1 and D2 but negative correlations with D3. High bio-deposited silica positively influenced micropore and mesopore development, while clay mineral compaction and dehydration transformations favored macropore development. Carbonate minerals primarily contributed to regular macropores, with complex correlations involving fractal dimensions D1, D2, and D3. The research results provide theoretical support for analyzing pore fractal characteristics of shallow old Marine shale reservoirs and the prediction and development plan of high-quality reservoirs of the Shuijingtuo Formation in the Yichang area.

Evaluation of different doses of dexmedetomidine for awake fibreoptic nasotracheal intubation in patients undergoing oromaxillofacial and oral malignancy surgeries: A randomised, double-blind study.

In patients undergoing cancer surgeries with anticipated difficult airway, awake fibreoptic nasotracheal intubation (AFONI) is critical for securing the airway. However, different doses of dexmedetomidine (DEX) are yet to be evaluated in these patients. Thus, we compared three doses of DEX for AFONI in patients undergoing oromaxillofacial and oral malignancy surgeries. In this randomised, double-blind study, 90 patients aged 18-60 years of either gender, with American Society of Anesthesiologists physical status I/II, and undergoing elective oromaxillofacial and oral malignancy surgeries were randomised to three groups: Group D1 (0.5 µg/kg DEX), Group D2 (1 µg/kg DEX), and Group D3 (1.5 µg/kg DEX). The primary outcome measure was the airway obstruction score. Secondary outcome measures were intubation scores (including vocal movement, coughing, and limb movements) and a 5-point fibreoptic intubation comfort score. Sedation was assessed using the Ramsay sedation score (RSS). One-way ANOVA and Chi-square test were used to assess the association between quantitative and qualitative variables, respectively. A P value of <0.05 was considered statistically significant. The airway obstruction score was comparable between the groups (P = 0.78). Similarly, vocal movement (P = 0.15), coughing (P = 0.31), limb movement (P = 0.51), and 5-point fibreoptic intubation comfort score (P = 0.49) did not differ between the groups. The mean RSS was significantly greater in Group D3 than in Groups D1 and D2 (P = 0.001). In combination with topical spray and airway block, all three doses of DEX resulted in comparable airway obstruction scores and thus provided favourable conditions for AFONI.

Linking metacercariae and adults of Microphallus basodactylophallus (Digenea: Microphallidae), based on larval stages from ctenophores and adult parasites from aquatic birds found in Mexico

Members of the genus Microphallus Ward, 1901, are endoparasites mainly of birds and mammals distributed worldwide. Unencysted metacercariae of Microphallus sp., were collected from the mesoglea of ctenophores of the genus Pleurobrachia Fleming; adult digeneans were recovered from the intestines of Eudocimus albus Linnaeus (Threskiornithidae) and Buteogallus urubitinga Gmelin (Accipitridae), in four locations from southeastern Mexico. Adult specimens were identified as M. basodactylophallus (Bridgman, 1969) based on the following features: body pyriform entirely covered by minute spines, prepharynx short, oesophagus very long, caeca short and widely divergent, testes slightly symmetrical and excretory vesicle short and V-shaped. Sequences from D1–D3 domain of the large subunit of ribosomal DNA (LSU) were generated, aligned, and compared with those of congeneric species available in GenBank. Phylogenetic analyses indicated that the metacercariae and adults formed a clade together with an isolate identified as M. basodactylophallus from Florida, USA (GenBank: AY220628). The intraspecific genetic divergence among isolates was low ranged from 0.0% to 0.6%, allowing the link between the two stages of the life cycle. We observed phenotypic plasticity in the morphological traits of M. basodactylophallus adults in definitive hosts (mammals and birds) throughout the distribution, which ranged from the USA to southeastern Mexico. Finally, the unencysted metacercariae identified as M. basodactylophallus represent the first report of a microphallid in ctenophores.

Boswellia carterii oleoresin extracts induce caspase-mediated apoptosis and G1 cell cycle arrest in human leukaemia subtypes.

Background: Leukemias are a common cancer in adults and children. While existing treatments are effective, they are associated with severe side-effects compounded by the emergence of drug resistance. This necessitates the need to develop new drugs and phytopharmaceuticals offer a largely untapped source. Oleoresins produced by plants in the genus Boswellia have been used for centuries in traditional medicine and recent work suggests they may exhibit anti-cancer activity. However, the underlying mechanisms remain unclear and most existing research focusses on Boswellia serrata; just one of many species in the Boswellia genus. To address these limitations, we elucidated the anti-cancer potential and associated mechanisms of action of Boswellia carterii. Methods: A methanolic solvent extraction method was optimised. The effect of methanolic extracts of B. carterii on leukaemia (K562, MOLT-4 and CCRF-CEM) and normal (PBMC) cell line viability was assessed using MTT assay and flow cytometry. Cell morphology, apoptosis (Annexin-V/propidium iodide), mitochondrial membrane potential (Rhodamine-123) and the cell cycle (propidium iodide) were evaluated using flow cytometry. Regulatory protein expression was quantified using Western Blot. Results: Methanolic extracts of B. carterii oleoresin reduced the viability of K562, MOLT-4 and CCRF-CEM cell lines with selectivity indexes of between 1.75 and 2.68. Extracts increased the proportion of cells in late apoptosis by 285.4% ± 51.6%. Mitochondrial membrane potential was decreased by 41% ± 2% and the expression of cleaved caspase-3, -7, and -9 was increased by 5.7, 3.3, and 1.5-fold respectively. Extracts increased the proportion of cells in subG1 and G1 phase by 867.8% ± 122.9% and 14.0 ± 5.5 and decreased those in S phase and G2/M by 63.4% ± 2.0% and 57.6% ± 5.3%. Expression of CDK2, CDK6, cyclin D1, and cyclin D3 were decreased by 2.8, 4.9, 3.9, and 2.5-fold. Conclusion: We are the first to report that methanolic extracts of B. carterii are selectively cytotoxic against three leukemia cell lines. Cytotoxic mechanisms likely include activation of the intrinsic apoptotic pathway and cell cycle arrest through downregulation of CDK2, CDK6, cyclin D1, and cyclin D3. Our findings suggest that B. carterii may be an important source of novel chemotherapeutic drugs and justifies further investigation.

Responsiveness of multiple patient-reported outcome measures for acute postsurgical pain: primary results from the international multi-centre PROMPT NIT-1 study

Responsiveness of multiple patient-reported outcome measures for acute postsurgical pain: primary results from the international multi-centre PROMPT NIT-1 study