Transcranial photobiomodulation add-on therapy to valproic acid for pentylenetetrazole-induced seizures in peripubertal rats.

BACKGROUND: Convulsive status epilepticus (CSE) prevention is critical for pediatric patients with epilepsy. Immediate intervention before CSE reduce severity. Despite its wide usage as an anticonvulsant, valproic acid (VPA) results in harmful side effects such as dose-dependent hepatotoxicity. Hence, reducing VPA dosage to minimize side effects while maintaining its efficacy is necessary, and transcranial photobiomodulation (tPBM) add-on therapy could facilitate this. We recently demonstrated for the first time that tPBM at a wavelength of 808 nm attenuated CSE in peripubertal rats. However, the effects of VPA with the add-on therapy of tPBM prior to seizures have not yet been explored. This study investigated whether adding tPBM to VPA exerts synergistic effect for CSE prevention in peripubertal rats. METHODS: A gallium-aluminum-arsenide laser (wavelength of 808 nm with an exposure duration of 100 s and irradiance of 1.333 W/cm2 at the target) was applied transcranially 30 min after VPA injection in Sprague Dawley rats. All the rats received 90 mg/kg of pentylenetetrazole (PTZ). Except for the saline (n = 3), tPBM + saline (n = 3), and PTZ group (n = 6), all the rats received a PTZ injection 30 min after VPA injection. The rats received add-on tPBM with PTZ immediately after tPBM. In the VPA + PTZ group, the rats received low-dose (100 mg/kg, n = 6), medium-dose (200 mg/kg, n = 6), and high-dose (400 mg/kg, n = 7) VPA. In the VPA + tPBM + PTZ group, the rats received low (100 mg/kg, n = 5), medium (200 mg/kg, n = 6), and high (400 mg/kg, n = 3) doses of VPA. Seizures were evaluated according to the revised Racine's scale in a non-blinded manner. RESULTS: Adding tPBM to low-dose VPA reduced the incidence of severe status epilepticus and significantly delayed the latency to stage 2 seizures. However, adding tPBM to high-dose VPA increased the maximum seizure stage, prolonged the duration of stage 4-7 seizures, and shortened the latency to stage 6 seizures. CONCLUSIONS: Adding tPBM to low-dose VPA exerted a synergistic prevention effect on PTZ-induced seizures, whereas adding tPBM to high-dose VPA offset the attenuation effect.

Use of dietary supplements containing polyvalent cations and antacids among people with HIV and its impact on viral suppression.

Dietary supplements and medications containing polyvalent cations can interact with integrase strand transfer inhibitors (INSTIs) and decrease exposure to INSTIs. In this cross-sectional study of 513 people with HIV (PWH) who were on stable antiretroviral therapy, 57.5% and 6.6% reported concurrent use of dietary supplements and antacids, respectively. In the multivariable analysis, the use of antacids, but not dietary supplements containing polyvalent cations, was associated with HIV viremia in PWH who received INSTI-based ART.

Bidirectional myofiber transition through altering the photobiomodulation condition.

Despite remarkable advancements in modern medicine, muscular atrophy remains as an unsolved problem. It is well known that pathological characteristics of different atrophy types could vary according to the pathophysiological causes. In fact, the lesion of atrophy is not always homogenously distributed but often predominantly evident in either fast or slow myofibers. As the focalization of the atrophic lesions, the existence and the functional impairment of each fast and slow progenitor/satellite cell (SC) are suspected though there are still controversies about this hypothesis. In this study, we isolated Pax7 positive (Pax7+ve) SCs from the tibia anterior (fast) and soleus (slow) muscles respectively and successfully demonstrated, for the first time, the difference between optimal exposure durations of photobiomodulation (PBM) which was known as low level laser irradiation (LLLI) in promoting proliferation of Pax7+ve SC which were acquired from fast and slow muscles respectively. Moreover, a hypertrophy-accompanied bidirectional change in myofiber composition with neuromuscular junction alteration, either from slow to fast or fast to slow, were achieved by applying different PBM durations. Simultaneously, PBM exhibited a synergistic effect with muscle exercise on the increase in myofiber size. Our data suggested the existence of at least two different populations of Pax7+ve SC which possess distinct sensitivities towards PBM. As our data revealed the capability of PBM in bidirectional changes of skeletal muscle composition and neuromuscular junction constitution thereby strengthen its contractility through altering the irradiation condition, we believe PBM showed the potential to be as a promising clinical treatment for muscular atrophy.

Micronized sacchachitin promotes satellite cell proliferation through TAK1-JNK-AP-1 signaling pathway predominantly by TLR2 activation.

BACKGROUND: Ganoderma sp., such as Ganoderma tsugae (GT), play an important role in traditional Chinese medicine. Ganoderma sp. contains several constituents, including Sacacchin, which has recently drawn attention because it can not only enhance the repair of muscle damage but also strengthen the muscle enforcement. Although Ganoderma sp. have a therapeutic effect for neuromuscular disorders, the underlying mechanism remains unclear. This study investigated the effect and underlying molecular mechanism of micronized sacchachitin (mSC) on satellite cells (SCs), which are known as the muscle stem cells. METHODS: The myogenic cells, included SCs (Pax7+) were isolated from tibialis anterior muscles of a healthy rat and were cultured in growth media with different mSC concentrations. For the evaluation of SC proliferation, these cultivated cells were immunostained with Pax7 and bromodeoxyuridine assessed simultaneously. The molecular signal pathway was further investigated by using Western blotting and signal pathway inhibitors. RESULTS: Our data revealed that 200 µg/mL mSC had an optimal capability to significantly enhance the SC proliferation. Furthermore, this enhancement of SC proliferation was verified to be involved with activation of TAK1-JNK-AP-1 signaling pathway through TLR2, whose expression on SC surface was confirmed for the first time here. CONCLUSION: Micronized sacchachitin extracted from GT was capable of promoting the proliferation of SC under a correct concentration.

A transient protective effect of low-level laser irradiation against disuse-induced atrophy of rats.

Satellite cells, a population of skeletal muscular stem cells, are generally recognized as the main and, possibly, the sole source of postnatal muscle regeneration. Previous studies have revealed the potential of low-level laser (LLL) irradiation in promoting satellite cell proliferation, which, thereby, boosts the recovery of skeletal muscle from atrophy. The purpose of this study is to investigate the beneficial effect of LLL on disuse-induced atrophy. The optimal irradiation condition of LLL (808 nm) enhancing the proliferation of Pax7+ve cells, isolated from tibialis anterior (TA) muscle, was examined and applied on TA muscle of disuse-induced atrophy model of the rats accordingly. Healthy rats were used as the control. On one hand, transiently, LLL was able to postpone the progression of atrophy for 1 week through a reduction of apoptosis in Pax7-veMyoD+ve (myocyte) population. Simultaneously, a significant enhancement was observed in Pax7+veMyoD+ve population; however, most of the increased cells underwent apoptosis since the second week, which suggested an impaired maturation of the population. On the other hand, in normal control rats with LLL irradiation, a significant increase in Pax7+veMyoD+ve cells and a significant decrease of apoptosis were observed. As a result, a strengthened muscle contraction was observed. Our data showed the capability of LLL in postponing the progression of disuse-induced atrophy for the first time. Furthermore, the result of normal rats with LLL irradiation showed the effectiveness of LLL to strengthen muscle contraction in healthy control.