bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementing with DHA and EPA alters metabolomic parameters in post‐menopausal women
Authors: Watkins Bruce A , Kim Jeffrey , Kenny Anne , Pedersen Theresa L , Li Yong , Pappan Kirk , Newman John W
Published: June 2021

Post‐menopausal women (PMW) are at a high risk of bone loss, exhibit hypertension and are likely marginal in n‐3 PUFA intakes. The purpose of our investigation was to characterize the oxylipins (OL), endocannabinoids (EC) and global metabolites (GM) in white PMW (75 ± 7 y, 26.5 ± 5 BMI and 40% hypertensive) from baseline to 6 mo. after receiving a supplement of LC (long chain) n‐3 PUFA (EPA and DHA). Plasma was extracted and subsequently analyzed for OL and EC using UPLC‐MS/MS and for GM by GC‐MS and LC‐MS/MS. Plasma fatty acids were determined by GC‐FID. The magnitudes of PUFA changes were influenced by baseline n‐3 PUFA status of the PMW. After supplementation, arachidonate‐derived diols were decreased and EPA and DHA diols, epoxides and alcohols were increased in PMW plasma. In addition, within the ECs measured, the LC n‐6 acyl‐ethanolamides were decreased and n‐3 PUFA increased, while only 2‐oleoly‐glycerol decreased after supplementation. The LC n‐3 PUFA supplementation increased steroid hormone levels, lysophospholipids, EPA and DHA but lowered AA after 6 mo. in PMW. We report findings on the OL, EC and GM in PMW that demonstrate responses to LC n‐3 PUFA intake from baseline. This research will likely help improve clinical evaluation of PMW and assessment of aging where the roles of dietary n‐3 PUFA are beneficial. (Supported by the Diet and Health Initiative, UConn)
Preliminary study on the intergerational effect of postnatal malnutrition on attention
Authors: Thomas Julian M , Zichlin Miriam L , Bryce Cyralene P , Galler Janina R
Published: June 2021

Early malnutrition has been associated with attention deficits across the lifespan. Limited studies exist on the intergenerational effects of malnutrition and, to our knowledge, none specifically address attention. In the current study, we assessed Barbadian adults (17–26y) whose mothers had been followed for 40y in the Barbados Nutrition Study (N=31). Eleven had mothers who suffered from a single episode of moderate‐ severe postnatal malnutrition in the first year of life (MAL). The remaining 20 were offspring of healthy mothers (CON) matched to the MAL group by age, sex, and handedness in childhood. The Conners Adult ADHD Rating Scale‐S:SV was used to identify inattention, hyperactivity, ADHD symptoms and DSM‐IV clinical index scores. Parental malnutrition effects were analyzed across factors, adjusting for childhood standard of living of the parent (SAS PROC MIXED). Mean scores were higher in the MAL offspring when compared with CON offspring, connoting more attention deficits. Significant main effects of nutrition were present for DSM‐IV clinical index scores (F=6.10, p<0.05). We concluded that postnatal malnutrition is associated with attention deficits in offspring of individuals exposed to postnatal malnutrition, though these offspring themselves were never malnourished. Studies in a larger sample are needed to identify biological and environmental mechanisms underlying these differences.

Grant Funding Source: NIH HD060986
Sweet‐baked products, but not whole or refined grains, are negatively associated with bone mineral density (BMD): the Framingham Offspring Cohort
Authors: Mangano Kelsey McKee , Sahni Shivani , Casey Virginia , Hannan Marian T
Published: June 2021

Objective

To determine whether whole grains (WG), refined grains (RG); sweet‐baked products (SW) affect BMD at femoral neck (FN), trochanter (TR) & lumbar spine (LS) in adults. To examine BMI as an effect modifier.

Methods

Multivariable regression assessed relations between WG, RG & SW (from FFQ 1995–98) with BMD in 1996–2001 among 2,657 Framingham Offspring participants, adjusting for covariates. Energy adjusted quartiles of WG, RG and SW were grouped as Q1 (low), Q2–Q3 and Q4 (high). Associations were stratified by BMI <25 or ≥ 25 kg/m2.

Results

Mean age 59y ± 9.5. Intakes of WG, RG, SW were 1.2 ± 1.2, 2.9 ± 1.7; 0.9 ± 1.1 servings/d. WG and RG were not linked with any BMD site (P range: 0.23–0.99). High SW intake was inversely related to FN‐BMD (P=0.03) & TR‐BMD (P=0.01) compared to Q1. In overweight group, high SW intake was inversely related to all BMD sites compared to Q1 (Table). Controlling for total fat or carbohydrate intakes (g/d) had no effect. No relation was seen in the normal weight group between BMD and WG, RG or SW.

Conclusions

SW intake was inversely related to hip and spine BMD in overweight adults, independent of total fat and carbohydrate.

Funding Source: NHLBI Framingham Heart Study (N01‐HC‐25195), Framingham Osteoporosis Study (NIH R01 – AR041398)

Grant Funding Source: NIH NIAMS
A study on the effect of breakfast skipping on dietary behavior among middle school students in Incheon, Korea
Authors: Chung Hyun‐Jung , Shim You‐Sun
Published: June 2021

This research was performed to provide basic data for the solution of skipping breakfast of middle school students in adolescence. The actual state of having breakfast, dietary life, eating habit and nutrition knowledge and the relationship between these factors and frequency of having breakfast were studied for 357 male middle school students in Incheon, Korea. As the results, the effective factors in skipping breakfast were related to family type, mother¡ s occupation, parent¡ s attitude toward skipping breakfast, and nutrition knowledge. Family type of single parent, no parents or with grand parents has low frequency of having breakfast (p<0.05). The frequency of having breakfast was low if a mother runs her own business and high if mother was professional or housewife (p<0.01). Skipping breakfast has close relationship with school activity, grades and eating habit. As the frequency of breakfast was high, the score of eating habit was high (p<0.001), and so was score of nutrition knowledge. To enhance adolescents¡ having breakfast rate, it is necessary that school nutrition teacher and local community perform a nutrition education for both students and their parents. This will make an education effective by connecting school and home education, to develop and provide various programs in nutrition education.
Hypoglycemic effect of Hedyotis diffusa in ob/ob mice
Authors: Kang Min‐Jung , Kim Jung‐In
Published: June 2021

Tight control of hyperglycemia is the main goal for the treatment of diabetes mellitus. The purpose of this study was to investigate the hypoglycemic effects of Hedyotis diffusa in an animal model of type 2 diabetes. Four‐week‐old ob/ob mice (n=14) were fed AIN‐93G diet or diet containing 1% ethanol extract of Hedyotis diffusa for 8 weeks after 1 week of adaptation. Serum glucose, insulin, and adiponectin levels were measured. Homeostasis model assessment‐insulin resistance (HOMA‐IR) was calculated by dividing the product of fasting insulin (μU/mL) and glucose (mmol/L) by 22.5. Consumption of Hedyotis diffusa significantly decreased serum glucose levels (p<0.05) and tended to decrease insulin levels compared with the control group. HOMA‐IR of Hedyotis diffusa group was significantly lower than the control group (p<0.05). Serum adiponectin levels of Hedyotis diffusa group were significantly higher than the control group (p<0.05). These results demonstrated that Hedyotis diffusa could improve glycemic control in an animal model of type 2 diabetes. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010–0011980).
The consumption of 12 eggs per week for 1 year significantly raises serum zeaxanthin levels with slight changes in macular pigment optical density and glare recovery in patients with early age‐related macular degeneration
Authors: Aljohi Hasan , Kotyla Elizabeth , Wilson Thomas A.
Published: June 2021

Age‐related macular degeneration (AMD) is a disease of the macula, which protects the retina from UV light damage. Eggs are rich source of lutein and zeaxanthin, two carotenoids that concentrate in the macula and protect it. Macular Pigment Ocular Density (MPOD) is a key diagnostic measurement in the development of AMD as well as the clinical eye exam. The purpose of this study was to determine whether consuming 12 eggs per week for 1 year raises serum lutein and zeaxanthin levels, increases MPOD, and slows down the progression of AMD in adults diagnosed with early to intermediate AMD. AMD was examined using 6 different clinical eye tests. Forty‐five adults were placed into the Intervention (n=27) or Control (n=18) group based on preference for consuming eggs. Serum zeaxanthin significantly increased (83%) in the Intervention but not in the Control after the 12 months. A non‐significant increase in serum lutein was also observed in the Intervention (52%) compared to the Control (6%) after the 12 months. The percent increase in MPOD was greater in the Intervention for the right (37% vs 14%) and in the left (42% vs 39%) eyes compared to the Control but not significantly. Glare recovery improved slightly in both eyes for the Intervention while it was significantly longer for the Control in the left eye (86% greater compared to the Intervention and a 32% decrease from baseline). No other vision changes were noted between the treatment groups. This study shows that while the consumption of 12 eggs per week for 1 year increases serum zeaxanthin, no significant changes were noted in MPOD and only glare recovery was improved in the Intervention. The Egg Nutrition Center of the American Egg Board and the Massachusetts Lions Eye Research Fund supported this research.
Dietary vitamin D3 supplementation at 50× the adequate intake decreases calbindin d28k and endoplasmic reticulum stress and increases apoptosis, suggesting toxicity, in the female transgenic G93A mouse model of amyotrophic lateral sclerosis
Authors: Taheri‐Shalmani Siavash , Shahsavar Shayan , Gianforcaro Alexandro , Solomon Jesse Adam , Hamadeh Mazen Jamal
Published: June 2021

Background

We previously showed that dietary vitamin D3 (D3) at 50× the adequate intake increased functional capacity in the transgenic G93A mouse model of amyotrophic lateral sclerosis (ALS), with females exhibiting signs of D3 toxicity. ALS is a progressive neuromuscular disease resulting in the death of upper and lower motor neurons.

Objective

In this pilot study, we analyzed the quadriceps of G93A mice following dietary D3 supplementation at 50× the AI for vitamin D receptor and markers of intracellular calcium trafficking (calbindin d28k, calretinin), endoplasmic reticulum (ER) stress (SERCA2, CHOP) and apoptosis (bax/bcl2 ratio, caspase 12 cleaved/pro ratio).

Methods

Beginning at age 25 d, 41 G93A mice were provided food ad libitum with either adequate (AI; 1 IU D3/g feed; 12 M, 11 F) or high (HiD; 50 IU D3/g feed; 10 M, 8 F) D3. At age 113 d, the quadriceps were analyzed for protein content. Differences were considered significant at P ≤ 0.10.

Results

In females, HiD had 33% lower calbindin d28k (P = 0.066), 68% lower CHOP (P = 0.074), and 242% higher bax/bcl2 ratio (P = 0.080) vs. AI. HiD males showed no significant differences vs. AI.

Conclusion

Dietary D3 at 50× the AI decreases ER stress in the quadriceps of female G93A mice, but increases apoptosis, which could be due to D3 toxicity. We hypothesize a dynamic crosstalk between ER stress and calcium trafficking. (Supported by NSERC and Faculty of Health, York University)

Grant Funding Source: NSERC and Faculty of Health, York University
Activation of Melanocortin Receptor 3 as a new strategy to control experimental and rheumatoid arthritis
Authors: Patel Hetal Brijesh , Bombardieri Michele , Pitzalis Costantino , Perretti Mauro
Published: June 2021

Study Objective

The anti‐inflammatory properties of melanocortin peptides have long been established, though their main molecular target(s) is still elusive. Two receptors (MC1R and MC3R) have been suggested as their main target, but the patho‐physiological impact of this important homeostatic anti‐inflammatory system is unclear: we focused here on experimental and rheumatoid (RA) arthritis.

Methods

Mouse Studies (1) Arthritis was induced by K/BxN serum transfer (200 μl) into wild type (WT), recessive yellow e/e (Mc1r inactive mutant) and Mc3r−/− mice and disease profiles monitored. (2) Gene expression analysis was performed in arthritic paw joints using qPCR. (3) Daily treatment with vehicle or D[Trp8]‐γ‐MSH (MC3R agonist) was given to WT and Mc3r−/− mice (20 μg) induced with K/BxN arthritis and disease profiles assessed. Human Studies qPCR was used to analyse MCR and/or pro‐inflammatory cytokine mRNA levels in RA synovium transplanted into SCID mice treated with D[Trp8]‐γ‐MSH.

Results

Upon K/BxN serum transfer, Mc3r−/− mice displayed a marked disease exacerbation whereas no different profile of disease development was displayed by the Mc1r mutant and WT mice. This heightened presence of disease in Mc3r−/− null mice was confirmed by histological analysis of paw joints. At peak of arthritic profile (D6), mRNA analysis revealed up‐regulation of Rankl, Mcp‐1, Nos2 and Il‐1β, Il‐6 in Mc3r−/− mice compared to WT. Treatment of arthritic mice with D[Trp8]‐γ‐MSH significantly attenuated disease. In another preclinical model, stimulation of human MC3R with D[Trp8]‐γ‐MSH inhibited human IL‐1β, IL‐6, TNF‐α and RANKL gene expression in RA synovium transplanted into SCID mice.

Conclusions

These findings identify MC3R‐mediated signaling as a novel anti‐inflammatory pathway for innovative therapeutic targeting in RA.
Cardiovascular Autonomic Activity Modulation By Nitric Oxide Synthases Mediates The Augmented Enalapril‐Evoked Hypotension In Ethanol‐Fed Female Rats
Authors: El‐Mas Mahmoud M , Abdel‐Rahman Abdel A
Published: June 2021

Chronic ethanol enhances the hypotensive action of enalapril in female rats. Here, we investigated whether cardiovascular auto‐nomic modulation by nitric oxide synthases (NOS) contributes to such enhancement. We investigated the effect of inhibition of eNOS [N5‐(1‐iminoethyl)‐L‐ornithine; L‐NIO], nNOS (Nω‐propyl‐L‐arginine; NPLA), or iNOS (1400W) on blood pressure (BP), myocardial contractility (dP/dtmax), and power spectral indices of hemodynamic variability in telemetered female rats fed with ethanol (5% w/v, 8 weeks) or control liquid diet in absence or presence of enalapril. In control rats, enalapril‐evoked hypotension was abolished by L‐NIO, but not by NPLA or 1400W, suggesting a preferential role for eNOS in this response. In ethanol‐fed, the greater enalapril hypotension was associated with reductions in (i) dP/dtmax, (ii) low‐frequency/high‐frequency ratio of interbeat intervals, suggesting cardiac parasympathetic dominance, and (iii) low‐frequency band of systolic BP, a marker of vasomotor sympathetic tone. While all NOS inhibitors attenuated the hemodynamic and autonomic responses of enalapril in ethanol‐fed rats, L‐NIO was the most efficacious in rectifying enalapril‐evoked autonomic responses. These findings implicate NOS isoforms, particularly eNOS, in autonomic imbalances that leads to the augmented enalapril hypotension in ethanol‐fed rats.
The ERK/MAPK‐Dependent Pressor Effect Of Intra‐RVLM Ethanol Is Tonically Attenuated By Local Phosphatases In Normotensive Rats
Authors: El‐Mas Mahmoud M , Abdel‐Rahman Abdel A
Published: June 2021

We recently reported that microinjection of ethanol into the rostral ventrolateral medulla (RVLM) elicits a modest pressor response in conscious normotensive rats. In this study, we tested the hypothesis that the RVLM phosphatase/extracellular signal‐regulated kinase (ERK) pathway modulates the pressor effect of ethanol. We show that the modest pressor response elicited by intra‐RVLM ethanol (10 μg) was: (i) abolished following local ERK inhibition with PD98059 (1 μg); (ii) associated with significant reduction in local phosphatase activity. Inhibition of the RVLM ser/thr phosphatase activity by okadaic acid (OKA, 0.4 μg) caused significant increases in blood pressure (BP) and potentiated the magnitude and duration of the pressor response as well as the phosphatase inhibition elicited by subsequent intra‐RVLM administration of ethanol. Intra‐RVLM acetaldehyde (2 μg), the main metabolic product of ethanol, caused no changes in BP or RVLM phosphatase activity but it produced significant increases in BP and inhibition of local phosphatase activity in OKA‐pretreated rats. Together, the RVLM phosphatase activity acts tonically to attenuate the ERK‐dependent pressor effect of ethanol or acetaldehyde in normotensive rats.
The role of MCT1 and MCT4 in drug‐induced muscle disorders
Authors: Leung Yat Hei , Lu Jennifer , Papillon Marie‐Ève , Bélanger François , Turgeon Jacques , Michaud Véronique
Published: June 2021

Background

Muscle injury, including myopathy, is a common side effect of some drugs, and particularly of statins. We hypothesized that these side effects are related to intracellular accumulation of lactic acid through monocarboxylate transporters, MCT1 and MCT4. Our objective was to investigate whether the transport of lactic acid is modulated by statins and other acidic drugs.

Methods

Cell lines used as models for MCT1 and MCT4 were Hs578T and MDA‐MB‐231, respectively. The cells were incubated with [14C]lactic acid at 37°C and the intracellular concentration of radioactive lactic acid was measured. Inhibition studies were conducted by co‐incubating the cells with different concentrations of acidic drugs (e.g. statins, gemfibrozil, irbesartan, losartan, valsartan, loratadine, ibuprofen, naproxen, and salicylic acid) and lactic acid.

Results

Atorvastatin and loratadine showed the highest inhibition with IC50 of 20 μM and 2μM, respectively. Fluvastatin and irbesartan showed an intermediate inhibition with IC50 of 100–1000 μM, while drugs such as lovastatin and NSAID showed low or no inhibition (IC50 >;1000 μM).

Conclusions

These results imply that atorvastatin and other acidic drugs can lead to the accumulation of lactic acid due to the blockage of MCT1 and MCT4. Further studies are required to link the intracellular accumulation of lactic acid and drug‐induced muscle pain.

Research supports; CIHR and HSF
Role of localized calcium events in regulation of vascular tone: A theoretical investigation
Authors: Parikh Jaimit , Kapela Adam , Tsoukias Nikolaos M
Published: June 2021

Localized calcium (Ca2+) events like sparks, puffs, pulsars and sparklets have been identified in the vascular cells. They have been suggested to play an important role in modulation of vessel tone. Theoretical modeling can provide quantitative insights and improve the fundamental understanding of the generation of these localized Ca2+ events. Hence we develop detailed finite element cellular models of Ca2+ dynamics and membrane electrophysiology in smooth muscle and endothelial cells. These models are integrated and modified to include myoendothelial projections with localized IP3 receptors, intermediate conductance Ca2+ activated potassium channels (IKCa) and TRPV4 channels. Activation of TRPV4 channels resulted in localized Ca2+ signals (sparklets). A single TRPV4 channel activation in absence of other channels and pumps resulted in localized calcium increase >;100nM and a spatial spread of ~ 6μm. The parameters of sparklets are affected by variety of factors of which open time of the channel, cooperative gating of the channels, diffusion coefficient of calcium and channel current can be the most important. The localized Ca2+ increase can activate IKCa channels and cause endothelium‐derived hyperpolarizing response modulating the vascular tone. The study provides a novel theoretical tool to examine the mechanisms behind localized calcium events and the regulation of vascular tone.

(Supported by NIH SC1HL95101).
MR or AT1R gene silencing in the PVN markedly attenuates Ang II‐induced hypertension in rats
Authors: Chen Aidong , Huang Bing S , Wang Hong‐Wei , Leenen Frans H.H.
Published: June 2021

Functional studies suggest that circulating Ang II activates an aldosterone‐MR‐endogenous ouabain (EO)‐ AT1R pathway in the hypothalamus and thereby causes hypertension. The present study examined whether intra‐PVN infusion of AAV‐MR‐siRNA or AAV‐AT1aR‐siRNA attenuates Ang II‐induced hypertension in rats. Two wks after bilateral intra‐PVN infusion of AAV‐MR‐siRNA (1 μl of 2.5 × 1010 genomic particles / ml), MR mRNA and protein expression in the PVN were reduced by 56% and 31% (P<0.01), compared with rats infused with AAV‐SCM‐siRNA. In 2nd set of rats, 1 week following bilateral intra‐PVN infusion of AAV‐MR‐siRNA, AAV‐AT1aR‐siRNA (1 μl of 2.5 × 1010 genomic particles / ml) or AAV‐SCM‐siRNA, Ang II was infused subcutaneously at 500ng/kg/min. After 2 weeks, AAV‐AT1aR‐siRNA significantly attenuated, whereas AAV‐MR‐siRNA largely prevented the Ang II‐induced hypertension. These results suggest that MR activation in the PVN plays a major role in Ang II‐induced hypertension, and genetic intervention of MR or AT1R production by AAV‐siRNA into specific nuclei provides new insights into the actual pathways of MR‐EO neuromodulation.

MAP (mmHg)
HR (bpm)

AAV‐SCM‐siRNA ( n=5)
113 ± 2
377 ± 8

AAV‐SCM‐siRNA +Ang II ( n=5)
192 ± 7 a
416 ± 15

AAV‐AT1aR‐siRNA+ Ang II ( n=7)
153 ± 8*, Δ
411 ± 12

AAV‐MR‐siRNA + Ang II ( n=7)
121 ± 6
377 ± 12

Data=means± SE.

p<0.05, vs. others,

p<0.05, vs. AAV‐SCM,

p<0.05, vs. AAV‐MR.

(Supported by grant # FRN:MOP‐74432 from the Canadian Institutes of Health Research)
Mice lacking the gene for Toll Like receptor‐4 (TLR4) had an attenuated blood pressure response to Angiotensin II infusion
Authors: Dange Rahul Babulal , Peng Hua , Feng Yumei , Francis Joseph
Published: June 2021

Hypertension (HTN) is considered as a low grade inflammatory disease. Previous studies from our lab indicate that brain inflammatory molecules contribute to the development of HTN. Since TLR4 is a major modulator of inflammation, in this study, we explored the role of TLR4 in angiotensin II (ANGII) induced HTN. TLR4 knock‐out (KO) and wild type (WT) mice were implanted with telemetry probes for mean arterial pressure (MAP) measurements. After collecting baseline MAP, osmotic minipump containing ANGII (200ng/kg/min) or saline was implanted for 14 days. Then the brains microdissected for the paraventricular nucleus (PVN), sub fornical organ (SFO), nucleus tractus solatorius (NTS) and ventrolateral medulla (VLM) and examined for the expression of prorenin receptor (PRR) and interleukin(IL)‐1β by RT‐PCR. In WT mice, ANG II infusion increased MAP by day 3 (122±4) and peaked on day 9 (145±2) and remained elevated. This was accompanied by an increase in IL‐1β and PRR in the SFO, PVN, VLM and NTS. In contrast, ANGII infusion in TLR4 KO did not increase MAP (96±2) and remained lower (97±2) when compared with WT+ANGII (144±3). In addition, there was decrease in the expression of PRR and IL‐1β in the brain regions of TLR4 KO after ANGII. These finding indicate that ANGII induced HTN is at least in part mediated by TLR4 expression in the pressor regions of the brain and is associated with increase in PRR and IL‐1β expression. Funding: LSU
5‐HT1A‐receptor (5‐HT1AR) modulate excitatory and inhibitory neuronal activity within the nucleus tractus solitarii (nTS)
Authors: Ostrowski Tim Daniel , Kline David D.
Published: June 2021

Activating central 5‐HT1AR increases respiration and induces hypotension and bradycardia. The nTS is the first central station for visceral afferent integration and critical for cardiorespiratory responses. Thus, we examined the modulation of synaptic transmission as well as nTS network activity by 5‐HT1AR in nTS neurons using the patch clamp technique. 5‐HT1AR were widely distributed within the nTS to cell bodies but not synaptic terminals. Activation of 5‐HT1AR by 10 μM 8‐OH‐DPAT decreased the amplitude of tractus solitarii‐evoked (TS‐)EPSCs, and decreased overall spontaneous excitatory nTS network activity. These effects persisted in the presence of GABAzine (25 μM) and were antagonized with co‐application of 5‐HT1AR blocker WAY‐100135 (10 μM). Blockade alone had no effect on TS‐EPSCs but increased excitatory network activity. On the other hand, nTS‐evoked (nTS‐) IPSCs did not change by activation of the 5‐HT1AR but spontaneous inhibitory nTS network activity decreased. Blocking 5‐HT1AR increased nTS‐IPSC and inhibitory network activity. Taken together, 5‐HT1AR are constitutively active within the nTS and their activation decreases afferent transmission as well as overall nTS network activity. These neurophysiological changes may explain the systemic effects seen with exogenous application of 5‐HT1AR agonists. Support: RO1 HL085108, RO1 HL098602, AHA 12POST11670002.
Vasorelaxant effect of chloroform extract from Justicia spicigera
Authors: Esquivel‐Gutiérrez Edgar , Noriega‐Cisneros Ruth , Villalobos‐Molina Rafael , Salgado‐Garciglia Rafael , Clemente‐Guerrero Mónica , Calderón‐Cortés Elizabeth , Saavedra‐Molina Alfredo
Published: June 2021

Hypertension remains, despite major advances in understanding its pathophysiology and therapeutic approach. One condition carries high morbidity and mortality worldwide and herbal medicine has gained ground in this area of medicine. In our group we are interested in some plants used in Mexico as alternative therapies for their possible antihypertensive properties. Previously, we tested four extracts from Justicia spicigera (hexane, chloroform, methanol and aqueous) known as Muicle in our region and the results shown that the chloroform extract has the best antihypertensive effect. The present study was designed to investigate if fractions from this extract could have a vasorelaxant effect to support our hypothesis. L‐NAME rats were used as an animal hypertensive model. The chloroform extract was fractionated in a chromatography column and collected in fractions, then were tested (0.1 – 1000 μg/mL) in phenylephrine‐precontracted endothelium‐intact aortic rings. The results suggest that the vasorelaxant effect is present in at least three fractions. The vasorelaxant effect was concentration‐dependent with EC50 = 1.1456 μg/mL ± 0.2440. The next step is to elucidate the mechanism to lower the blood pressure and if some component of the extract is the responsible for this effect.
NOVEL ROLES FOR IGF‐1 IN CEREBROVASCULAR AND BRAIN AGING
Authors: Sonntag William E
Published: June 2021

Insulin‐like growth factor (IGF)‐1 is an important neurotrophic hormone. Deficiency of this hormone has been reported to influence the genesis of cognitive impairment and dementia in rodent models of aging and in elderly patients. However the specific mechanisms for these effects remain unclear. The regulation of IGF‐1 is complex and endocrine, paracrine and autocrine actions have been reported. Using both growth hormone and IGF‐1 deficient rats and igff/f mice treated with AAV‐Cre vectors to provide conditional and temporal knockout of IGF‐1, we find that both the vascular actions of IGF‐1 and the synaptic effects of IGF‐1 are important for the cognitive effects of IGF‐1. IGF‐1 appears to regulate both cerebrovascular density and myogenic constriction and protects against the deleterious effects of hypertension. In addition, IGF‐1 has important effects on synaptic proteins involved in exocytosis. The emerging data indicate that endocrine and paracrine IGF‐1 may have synergistic action on each of these targets and age‐related changes in each compartment have specific actions important for brain aging. Further studies that detail the specific actions of this important neurotrophic hormone will likely lead to therapies that result in improved cognitive function for the elderly patients.
The ventilatory response to muscle metaboreflex stimulation in patients with COPD
Authors: Bruce Richard Michael , Turner Alice , White Michael John
Published: June 2021

The role of skeletal muscle metaboreceptive afferents in human cardiorespiratory control can be examined using post exercise circulatory occlusion (PECO). We have shown that the ventilatory responses to PECO are augmented in humans during concurrent hypercapnia. We now aim to determine whether PECO produces ventilatory responses in COPD patients who do and do not retain CO2.

With Ethical approval, 18 COPD patients and 9 aged matched controls performed 2 trials. In both trials participants rested for 2 minutes followed by 2 minutes of rhythmic handgrip exercise. Upon cessation of exercise in the PECO trial a cuff around the upper arm was inflated to 200mmHg for 2 minutes before cuff deflation.

PECO maintained blood pressure significantly above baseline levels in COPD patients and control participants (+ 7 mmHg and + 8 mmHg respectively). However ventilation during PECO was only maintained above baseline levels in COPD patients (+2–3 l.min‐1). There was no difference in this response between retainers and non‐retainers of CO2.

These results suggest that metaboreflex activation causes ventilatory responses in patients with COPD but not in healthy aged matched controls. However as there was no difference in the ventilatory response to PECO in CO2 retainers and non‐retainers it appears that chronic hypercapnia is not the underlying mechanism behind the response.
Sex‐based comparisons in oxidative DNA damage following 2h moderate cycling exercise
Authors: Yasuda Nobuo , Tanioka Toshihiro
Published: June 2021

The purpose of the study was to determine the effects of 2h moderate cycling exercise on whole body oxidative DNA damage and repair in men and women. Recreationally active men (M, n=13; age: 19.9±1.4 year; height: 171.2±3.6 cm; body weight: 67.5±11.9 kg; body mass index: 23.0±3.5 kg/m2; body fat: 15.1±6.6 %) and women (W, n=12; 20.±90.3 year; height: 160.1±5.6 cm; body weight: 54.7±5.8 kg; body mass index: 21.3±1.8 kg/m2; body fat: 21.7±3.0 % [mean±SD]) served as the subjects. Before (Pre) and after (immediately Post and Post 24 hours) 2h cycling exercise at 60% VO2 peak, spot urine samples were collected for later analysis of 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) determined with high performance liquid chromatography. With regard to 8‐OHdG level (ng/mg Creatinine), two‐way (time × sex) analysis of variances (ANOVA) showed no significant main effects for time, sex or interaction (Pre: 3.0±1.2, Post: 3.6±1.2, Post‐24h: 3.2±1.1 for M; Pre: 3.2±1.2, Post: 3.5±1.1, Post‐24h: 3.2±0.9 for W). However, there was a tendency for 8‐OHdG to be higher following exercise and return to the baseline level at Post‐24h in both men and women. These findings indicate that men and women show similar whole body DNA damage and repair after 2h moderate cycling exercise, which appears not to induce cumulative harmful oxidative stress.

Supported partly by funds from the Grant‐in‐Aid for Scientific Research (C) in Japan (Grant No.23500867).
Casein peptide supplementation enhances training effects on mitochondrial biogenesis of skeletal muscle in mice
Authors: Matsunaga Yutaka , Tamura Yuki , Masuda Hiroyuki , Takahashi Yumiko , Hoshino Daisuke , Hatta Hideo
Published: June 2021

Aims

Casein peptide consists of few amino acids. Previous studies reported that oral amino acid supplementation enhanced training effects and endurance performance. However, effects of peptide supplementation are unclear. Therefore, the aim of this study was to determine whether peptide supplementation enhances training effects on mitochondrial biogenesis of skeletal muscle.

Methods

6weeks old male ICR mice were randomly assigned to casein peptide (0.2 mg/g BW) ingestion group (CP) or equal amount of water ingestion group (CON). They were provided with high fat diet (56.7% fat) ad libitum and ingested either casein peptide or water (7 times/week) 30 min before endurance training (20–25 m/min×60 min, 5 times/week, for 6 weeks). All mice were sacrificed 48 h after the last training session. Muscle glycogen concentrations, muscular citrate synthase (CS) and β‐hydroxyacyl‐CoA dehydrogenase (β‐HAD) activities, which are mitochondrial enzyme activity, were measured.

Results

Muscle glycogen concentrations were higher in CP group than in CON group (p<0.05). Muscular citrate synthase activity was significantly higher in CP group than in CON group (p<0.05) and β‐HAD activity tended to be higher in CP group than in CON group (p=0.08).

Conclusion

Casein peptide supplementation enhances training effects on mitochondrial biogenesis of skeletal muscle in mice. Supported by Morinaga Milk Industry CO., LTD.
Establishment of a cell‐free bioassay for detecting dioxin‐like compounds
Authors: Tsai Tzu‐Ching , Wang Bo‐Jeng , Lee Hsinyu
Published: June 2021

Dioxins are byproducts from incomplete combustion processes and belong to a group of mostly toxic chemicals known as persistent organic pollutants, and 2, 3, 7, 8‐tetrachlorodibenzo‐p‐dioxin (TCDD) is considered to be the most toxic species of all dioxin‐like compounds. Analytical chemical processes are employed to determine the specific dioxin content in environmental samples. However, cost‐ineffectiveness and excess time consumption limit their routine utilization. The aryl hydrocarbon receptor (AhR) is the major TCDD receptor. Upon binding to dioxin, the AhR dissociates from Hsp90 and other cofactors. TCDD‐bound AhR subsequently translocates to the nucleus and interacts with the AhR nuclear translocator (Arnt) to induce signal transduction. Here, we describe a highly sensitive and cost‐effective alternative assay based on detecting stability of bioluminescence signals. We generated AAPA cells that stably coexpress Renilla luciferase tagged‐AhR (AhR‐RL), Ah receptor‐interacting protein (AIP), p23 and yellow fluorescent protein‐tagged Arnt (Arnt‐YFP). Treatment with 3‐methylcholanthrene (3MC), a dioxin agonist, enhanced the interaction between AhR and Arnt and avoided proteosomal degradation. In addition, treatment with 3MC and TCDD stabilized Renilla luminescence in AhR‐RL of AAPA cell‐free extracts in a concentration‐dependent manner. The TCDD detection limit in this cell‐free system was as low as 10−18 M. These results highlight the potential of AAPA cell‐free extracts to detect dioxin‐like pollutants.
New, puzzling insights on the old and unsolved forelimb/hindlimb enigma: comparative evolutionary myological studies
Authors: Diogo Rui , Linde‐Medina Marta
Published: June 2021

Most textbooks and papers state that the structures of the tetrapod fore and hindlimb are serial homologues but these statements seem to be due to a confusion between the serial homology of the vertebrate pelvic and pectoral appendages as a whole and of their structures, leading to a crucial question being overlooked: why are the skeletal and particularly the muscle structures of the fore and hindlimb actually so strikingly similar to each other? We provide an updated discussion of these questions and present a surprising and puzzling result of our comparative myological studies: in humans the number of forelimb muscles/muscle groups with clear ‘equivalents’ in the hindlimb (19) is actually substantially higher than in taxa such as rats (14), lizards (14) and even salamanders (18). Furthermore, at least five of the 19 modern human adult forelimb elements that have a clear hindlimb ‘equivalent’ derive from embryonic anlages that are very different from the ones giving rise to their adult hindlimb ‘equivalents’. These data contradict the hypothesis that the similarity in muscle structures between the forelimb and hindlimb of tetrapods such as modern humans are due to their origin as serial homologues; this similarity is instead the result of phylogenetically independent evolutionary changes leading to a parallelism/convergence due to developmental, functional constraints, topological and phylogenetic constraints.

Grant Funding Source: Start‐up package of Howard University College of Medicine
Detection of DNA damage in brown bullhead fish from Lake Erie using comet assay
Authors: Harmon Juliane E. , Diegelman‐Parente Amy
Published: June 2021

Presque Isle Bay is shallow freshwater ecosystem located off the coast of Erie, Pennsylvania. Bounded on the north and west sides by a recurved peninsula which is home to Presque Isle State Park, Presque Isle Bay was listed as an Great Lakes Area of Concern (AOC) in 1991 primarily based on observations of external fish tumors on brown bullhead (Ameiurus nebulosus) collected from the Bay area. Limited findings on the causative agents for these lesions as well as no evidence that these tumors adversely affect survival, growth, or reproduction of this species of fish have left many questions unanswered two decades later. The comet assay determines a qualitative level of DNA damage from cells obtained from blood or tissue samples. This is accomplished by electrophoresis of whole cells fixed to a microscope slide with subsequent analysis using fluorescence microscopy. The extent of DNA damage is directly proportional to the amount of “tail” seen in the dye‐stained DNA comet. In this research project, we have used a comet assay to assess the level of DNA damage within various biological samples isolated from brown bullhead collected within and external to the bay area. While this has not identified the causative agent of DNA damage, it has provided additional information regarding the skin tumors observed on these fish. Research support provided to A.D‐P through a Research Science Consortium Grant from the Tom Ridge Environmental Center and a Mercyhurst University Academic Enrichment Grant.
Vasoactive intestinal peptide (VIP) is chemoattractant for resting, mouse T cells by upregulating the epidermal growth factor receptor (EGFR) pathway
Authors: Wanjara Steve Biko , Dorsam Glenn P
Published: June 2021

Effective immune protection against enteric pathogens is critical for the survival of the mammalian host. The human gut is home to nearly 100 trillion microorganisms consisting of ≈1000 distinct bacterial species, some of which are life‐threatening if they escape the gut lumen. Recruitment of peripheral, naïve T Lymphocytes to the gut replenishes this organ with regulatory T cells and folicular helper T cells, as well as assisting in B cell activation within specilizaed gut‐lymphoid regions, called Peyer's Patches. A potent T cell chemoattractant, called vasoactive intestinal peptide (VIP), is secreted by a dense network of nerves innervating the gut. Importantly, the removal of VIP receptors expressed on T cells causes a drastic reduction in recruited gut T cells supporting a role for this signaling axis in T cell trafficking to this organ. However, the molecular mechanism controlling T cell homing to the gut by VIP is presently unknown. We hypothesized that VIP signaling upregulates an epidermal growth factor receptor (EGFR) signaling pathway, based on a previously published global microarray study by our laboratory. Using primary, resting mouse CD4 T cells, we tested whether a coordinated upregulation of this EGFR pathway occurred by qRT‐PCR. This analysis showed a rapid, transient and coordinated upregulation of the EGFR pathway ≤ 2.5 hours post‐exogenous VIP treatment. Collectively, we conclude that VIP signaling initiates a chemoattractant cellular program through the coordinated upregulation of the EGFR pathway. Future research will be required to directly test whether this mechanism controls resting T cell trafficking to the gut.
Biomarkers of acute rejection in renal transplant: a proteomic approach
Authors: Perez Juliana Dineia , Sakata Maisa Mayumi , Cunha Tatiana Sousa , Arita Danielle Yuri , Colucci Juliana Almada , Junior Helio Todesco Silva , Pestana Jose Osmar Medina , Casarini Dulce Elena
Published: June 2021

Kidney transplant is the best treatment for patients with end stage renal failure. Acute rejection (AR) is the major impediment to success in renal transplantation. We aimed to identify biomarkers candidates for acute renal rejection using plasma using LC‐MSE.

Analysis was performed with plasma from 25 renal transplant patients with stable renal graft function ‐ control group (Ct) ‐ and 9 patients with acute graft rejection ‐ rejection group (Rej).

We have detected 19 proteins overexpressed in the Rej group compared to Ct group, 02 proteins were underexpressed and 04 that were present only in the Rej group. Among the 19 overexpressed proteins we have selected 03 candidates for AR biomarkers in this model of renal graft. This overexpression was confirmed by Western Blotting. They are: alpha‐1 antitrypsin (A1AT) also known as SERPIN1, alpha‐2 antiplasmin (A2AP) called SERPINF2 and serum amyloid A (SAA). These proteins are involved in the acute phase response and are strongly associated among itself. With this study we identified a number of new targets in plasma that can be used in the future to monitor the patient. These proteins may be validated in the future as markers of acute rejection in renal transplantation. This is the first study using the technique of LC‐MSE to investigate proteomic changes in plasma of kidney transplant patients. (Supported Fapesp).
The role of PML in oxidative stress responses
Authors: Guo Shuang , Cheng Xiwen , Kao Hung‐Ying
Published: June 2021

Oxidative stress is a consequence of an imbalance between reactive oxygen species (ROS) production and the ability of cytoprotective system to detoxify the reactive intermediates. Nuclear factor erythroid 2‐related factor 2 (Nrf2) is a transcription factor that plays essential roles in trans‐activating cytoprotective genes via binding to the antioxidant response elements (AREs) in their upstream promoter regions. Promyelocytic leukemia protein (PML), a tumor suppressor protein, is down‐regulated in many cancer types. Using biochemical, molecular and cellular biology techniques and animal tissues, we investigated the role of PML in oxidative responses. We show that PML negatively controls protein abundance and trans‐activating capacity of Nrf2. Mitochondrial defects observed in tissues isolated from PML−/− mice contribute to ROS elevations and Nrf2 activations. We also demonstrate that sulforaphane (SFN), an antioxidant, regulates Nrf2 activity through controlling subcellular distribution of PML. Taken together, we have uncovered a novel regulatory mechanism in which PML functions as an oxidative sensor to regulate the expression of antioxidant genes through regulation of Nrf2 activity.

This study is supported by NIH R01 DK078965 and HL093269.
HMG box‐containing protein 1 (HBP1) as a downstream signaling effector of EGFR in oral cancer
Authors: Chan Chien‐Yi , Lee Ming‐Fen , Huang Shih‐Yi , Chou I‐Tai , Lin Tzu‐Yuan , Huang Chun‐Yin
Published: June 2021

Aberrant activation of the epidermal growth factor (EGF) receptor (EGFR) signaling in the squamous cell carcinomas of the head and neck (SCCHN) is often associated with inauspicious prognosis and low survival. Transcription factor HMG box‐containing protein 1 (HBP1) functions as a potential tumor repressor in various cancers; however, its role in oral cancer is still unclear. Analysis of human oral cancer specimens revealed that the mean HBP1 mRNA level in tumors was significantly lower than that of the normal tissues, and that the concurrent status of low HBP1 and high EGFR was associated with the invasiveness of oral cancer. To explore the potential link between EGFR signaling and HBP1, we treated EGFR‐overexpressing oral cancer cell lines, HSC‐3 and FaDu, with EGFR inhibitors, AG1478 and Erlotinib, or EGFR siRNA, and found that EGFR down‐regulation increased HBP1 expression. Administration of phosphatidylinositol 3‐kinase (PI3K) inhibitor, Ly294002, decreased Akt phosphorylation and increased HBP1 expression. Overall, the expression of Akt and HBP1 acted in a reciprocal manner. Moreover, HBP1 knockdown in HSC‐3 cells enhanced in vitro colony formation and in vivo xenograft tumor growth. HBP1 knockdown attenuated Erlotinib‐mediated cyclin D1 reduction and subsequent G1 arrest. Together, our data reveal a novel role of HBP1 as a downstream effector of the EGFR/Akt signaling pathway in oral cancer.
Heavy Metals and Microbial Contents of Roadside Roasted Corn and Plantain
Authors: Oyelola Olukemi Taiwo , Afolabi Miriam , Ajiboshin Isaac , Ofodile Nwannemka , Banjoko Immaculata
Published: June 2021

In Nigeria, West Africa, it is common practice to eat roasted food as snacks without being mindful of the health implications from the environment where it is roasted. This research work evaluated the level of heavy metals and microbial contents in roadside roasted corn and plantain from three locations in the Alimosho Local Government Area of Lagos State. Heavy metals and microbial concentration of 18 samples were analyzed using the Atomic Absorption Spectrophotometry (AAS) and Standard Microbiological Techniques (SMT). The average concentration of heavy metals in all the samples ranged between 0.45 – 1.40mg/g, 2.45 – 4.80mg/g, 3.20 – 14.05mg/g and 9.95–18.05mg/g for copper, zinc, iron, and magnesium respectively. Furthermore, samples from heavy traffic areas had average concentration range of between 0 – 58.40mg/g and 0 – 1.95mg/g for lead and cadmium respectively. Most of the values are higher than World Health Organization permissible limits. The average microbial load of the samples ranged between 250×10−3 – 800×10−3 Cfu. Samples from locations close to refuse dumpsite had the highest microbial content. Four micro organisms isolated from the samples are Escheriachia coli, Bacillus species, Neurospora species and Aspergillus niger. These findings indicate that roadside roasted food are contaminated by the polluted environment which make them not healthy for human consumption.
Acute appetite responses to two different dietary fibers as part of ready‐to‐eat breakfast cereals in overweight women
Authors: Lafond David W , Rains Tia M. , Cook Chad M. , Maki Kevin C. , Schild Arianne L. , Kaden Valerie N. , Kelley Kathleen M. , Lawless Andrea L. , Romsos Dale R.
Published: June 2021

High‐fiber foods have been shown to increase post‐meal satiety compared to similar foods with less fiber. The objective of this study was to evaluate the effects of two dietary fibers, in ready‐to‐eat (RTE) cereals, on subjective appetite and energy intake at a subsequent meal. Thirty‐six overweight women (24.3±0.5 y; BMI 27.4±0.3 kg/m2) consumed four RTE cereals on separate days in random order. Amount consumed was normalized to 500 g using 2% milk and water. Test cereals provided an additional 14.9 g dietary fiber from hydrolyzed wheat arabinoxylan (345 kcal) or intact flax fiber (347 kcal) vs. a low‐fiber control matched for protein and fat with higher available carbohydrate (control A; 4 g fiber; 460 kcal) and a low‐fiber energy matched control (control B; 3 g fiber; 341 kcal). Visual analog scale appetite ratings were measured every 15 min for 240 min. An ad libitum macaroni and cheese lunch was provided at 240 min. No differences were observed between conditions in appetite ratings or energy intake at lunch. RTE cereal+lunch total energy intake (kcal) for the wheat (907±37), flax (894±36), and control B (899±38) conditions were significantly lower than control A (994±37, p≤0.006 for each). These results suggest that increasing the fiber content of RTE cereals at breakfast reduces energy density without increasing appetite throughout the morning, or food intake at a subsequent meal. Supported by Kellogg Company