Increasing Natural Killer Cell Activity of Mineral Nanomaterial ALP1018 in Healthy Adults: A Randomized, Double-Blind, Placebo Comparative Clinical Trial.

This randomized, double-blind, placebo comparative clinical trial aimed to determine the immune-enhancing effects and safety of a nanomaterial with iron and zinc (ALP1018) in healthy adults. Participants who met the inclusion criteria were recruited for this study (n = 80) and randomly assigned to either the test group (n = 40), which was given Alp1018 in capsule form, or the placebo group (n = 40), which was given crystal cellulose capsules of identical appearance, weight, and flavor for 8 weeks. Compared to baseline, natural killer (NK) cell activity (%) increased in the test group after 8 weeks, although there were no changes in the placebo group. Furthermore, in the subgroup analysis of Coronavirus disease 2019 (COVID-19) affected participants, significantly increased NK cell activity was observed in the test group at 4 (p < 0.05) and 8 weeks (p < 0.05). No significant differences were observed in cytokine levels between the two groups. ALP1018 supplementation appeared to enhance immune function by improving NK cell activity without adverse effects in healthy adults.

In vitro and in vivo genotoxicity evaluation of ALP1018, a nanomineral food supplement.

The use of nano-based dietary supplements is increasing around the world, as nanotechnology can help enhance nutrient bioavailability. ALP1018 is a newly developed iron-zinc complex supplement designed as a nanoformulation to improve the efficacy of iron and zinc supplementation. However, safety concerns have been raised, as there is no clear evaluation of ALP1018 toxicity. The goal of this study was to determine the potential mutagenicity and genotoxicity of ALP1018 through three standard screenings: the Ames test, which evaluates bacterial reverse mutations; the in vitro test of chromosomal aberration in Chinese hamster lung cells; and the in vivo micronucleus assay using ICR mice. ALP1018 showed no mutagenic effect, as no increase was observed in the presence or absence of metabolic activation (S9 mix) in revertant colonies on all the bacterial strains used in the Ames test. No structural chromosomal abnormalities were observed in the presence or absence of the S9 mix in mammalian cells used in the chromosomal aberration assay. In the micronucleus test, the frequency of micronucleated polychromatic erythrocytes was not significantly increased in mouse bone marrow cells. Based on these findings, we can conclude that ALP1018 is safe to use and has no mutagenic or genotoxic potential.

Anti-Proliferative Effect of Allium senescens L. Extract in Human T-Cell Acute Lymphocytic Leukemia Cells.

Allium species are well known plants distributed throughout the world, and they contain various bioactive components with different biological activities including anti-cancer effects. In this study, we investigated the inhibitory effect of Allium senescens L. (A.S.) extract on cell survival and IL-2-mediated inflammation in human T cell acute lymphocytic leukemia (T-ALL) Jurkat cells. Our results showed that A.S. extract induced caspase-dependent apoptosis of Jurkat cells with no significant cytotoxicity in the normal peripheral blood mononuclear cells. A.S. extract induced ROS generation through the activation of MAPK p38 phosphorylation. It also inhibited IL-2 mRNA expression and NF-κB signaling mediated by phorbol 12-myristate 13-acetate, and phytohemagglutinin. Combined treatment with A.S. extract and axitinib/dovitinib exerted enhanced inhibitory effects on T-ALL cell growth and IL-2 production. These results provide novel information on the potential use of A.S. extract as a therapeutic herbal agent for the treatment and prevention of T-ALL.

In vitro combinatorial anti-proliferative and immunosuppressive effects of Brucea javanica extract with CX-4945 and imatinib in human T-cell acute lymphoblastic leukemia cells.

Since 1970, the isolated and identified components of Brucea javanica (L.) Merr. have been known to contain anticancer effects, particularly antileukemic effect. In this study, the inhibitory effect of Brucea javanica (BJ) on cell growth and inflammation was confirmed in human T-cell acute lymphocytic leukemia (T-ALL) cells, and its efficacy as an antileukemic agent was verified. Our results showed that BJ extract induced caspase-dependent apoptosis of T-ALL Jurkat cells through inhibition of the CK2-mediated signaling pathway, while exerting no significant cytotoxicity in normal peripheral blood mononuclear cells. Moreover, BJ extract suppressed the NF-κB signaling pathway, thus, inhibiting the interleukin (IL)-2 expression induced by phorbol 12-myristate 13-acetate (PMA) and phytohemagglutinin (PHA). Notably, combined treatment with BJ extract plus CX-4945 or imatinib exerted enhanced inhibitory effects on T-ALL cell growth and IL-2 production. Overall, these results suggest that BJ extract can be a potent therapeutic herbal agent for T-ALL treatment and prevention of IL-2 mediated inflammatory immune responses.

Factors influencing healthcare utilization among children with pneumonia in Muntinlupa City, the Philippines.

We evaluated the factors influencing healthcare utilization among children aged < 5 years with pneumonia symptoms in Muntinlupa City, the Philippines. We interviewed 1,330 caregivers from 190 households per district in seven districts from March to April, 2009 using a standardized questionnaire to obtain information about demographic characteristics, access to healthcare facilities, and potential barriers to healthcare utilization. The mean age of the children was 32 months; 54.7% were boys. Seventy-four point three percents (n = 972) of caregivers stated when their child had pneumonia symptoms they brought them to a government health center, 14.1% (n = 184) went to a private clinic, 8.0% (n = 104) went to a hospital, 3% (n = 40) were treated at home and 0.5% (n = 7) received traditional medicine from a local healer. Caregivers required an average of 12 minutes to reach a healthcare facility. Reasons given by caregivers for their choice of healthcare facility were low cost (47.5%), availability and accessibility to transportation (29.6%) and perceived good quality of care (16.5%). In conclusion, nearly three quarters of caregivers interviewed brought their child with pneumonia symptoms to a government health center for treatment. Cost was the main factor influencing choice, followed by transportation availability and quality of care.

Acupuncture stimulation of the vision-related acupoint (Bl-67) increases c-Fos expression in the visual cortex of binocularly deprived rat pups.

Our previous study with functional magnetic resonance imaging (MRI) demonstrated that acupuncture stimulation of the vision-related acupoint, B1-67, activates the visual cortex of the human brain. As a further study on the effect of B1-67 acupuncture stimulation on the visual cortex, we examined c-Fos expression in binocularly deprived rat pups. Binocular deprivation significantly reduced the number of c-Fos-positive cells in the primary visual cortex, compared with that of normal control rat pups. Interestingly, acupuncture stimulation of B1-67 resulted in a significant increase in the number of c-Fos-positive cells in the primary visual cortex, while acupuncture stimulation of other acupoints less important for visual function had no significant effect on c-Fos expression in the primary visual cortex. The results suggest the possibility of vision-related acupoint (B1-67) having an influence over the activity of the primary visual cortex.

Decrease of the electroacupuncture-induced analgesic effects in nuclear factor-kappa B1 knockout mice.

To investigate the involvement of nuclear factor kappa B1 (NF-kappaB1; p50/p105) in electroacupuncture (EA)-induced analgesia, 2 and 100 Hz EA stimulations were applied at acupoint ST36 (Zusanli) in NF-kappaB1 knockout mice. EA was performed for 30 min and tail-flick latencies (TFLs) were evaluated every 15 min for 1 h. Wild-type mice displayed a 63.3% increase in TFLs compared to baseline after 2 Hz EA, whereas NF-kappaB1+/- mice exhibited a 41.8% increase and NF-kappaB1-/- mice showed only a 3.9% increase of TFLs. The TFLs of 100 Hz EA showed similar trends: a 72.6% increase of TFLs in wild-type, a 38.6% increase in NF-kappaB1+/- and a 9.3% increase in NF-kappaB1-/- mice. The present findings suggest that NF-kappaB1 may play a crucial role in both low and high frequency EA-induced analgesic effects.

Acupuncture enhances cell proliferation in dentate gyrus of maternally-separated rats.

Maternal separation in early life can increase vulnerability to neuropsychiatric disorders over the lifespan. To investigate the effect of acupuncture on cell proliferation in the dentate gyrus (DG), 5-bromo-2'-deoxyuridine (BrdU)-immunohistochemistry was performed in maternally-separated rat pups. Maternal separation, for 7 days from postnatal day 14, induced a significant decrease of BrdU-immunoreactive cells in DG, while acupuncture treatment at acupoint Shenmen (HT7), at the end of the transverse crease of the ulnar wrist, resulted in the significant increase in the number of BrdU-positive cells in DG. However, acupuncture at acupoint ST36, near the knee joint, produced no increase in the number of BrdU-positive cells. These findings indicate that acupuncture at acupoint HT7 appears to stimulate cell proliferation, and we suggested that acupuncture may be useful in the treatment of diseases related to maternal separation.