AMP-activated protein kinase (AMPK) activators have garnered significant attention for their potential to prevent the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) into liver fibrosis and to fundamentally improve liver function. The broad spectrum of pathways regulated by AMPK activators makes them promising alternatives to conventional liver replacement therapies and the limited pharmacological treatments currently available. In this study, we aim to illustrate the newly detailed multiple mechanisms of MASLD progression based on the multiple-hit hypothesis. This model posits that impaired lipid metabolism, combined with insulin resistance and metabolic imbalance, initiates inflammatory cascades, gut dysbiosis, and the accumulation of toxic metabolites, ultimately promoting fibrosis and accelerating MASLD progression to irreversible hepatocellular carcinoma (HCC). AMPK plays a multifaceted protective role against these pathological conditions by regulating several key downstream signaling pathways. It regulates biological effectors critical to metabolic and inflammatory responses, such as SIRT1, Nrf2, mTOR, and TGF-β, through complex and interrelated mechanisms. Due to these intricate connections, AMPK’s role is pivotal in managing metabolic and inflammatory disorders. In this review, we demonstrate the specific roles of AMPK and its related pathways. Several agents directly activate AMPK by binding as agonists, while some others indirectly activate AMPK by modulating upstream molecules, including adiponectin, LKB1, and the AMP: ATP ratio. As AMPK activators can target each stage of MASLD progression, the development of AMPK activators offers immense potential to expand therapeutic strategies for liver diseases such as MASH, MASLD, and liver fibrosis.

AMP-activated protein kinase (AMPK) activators have garnered significant attention for their potential to prevent the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) into liver fibrosis and to fundamentally improve liver function. The broad spectrum of pathways regulated by AMPK activators makes them promising alternatives to conventional liver replacement therapies and the limited pharmacological treatments currently available. In this study, we aim to illustrate the newly detailed multiple mechanisms of MASLD progression based on the multiple-hit hypothesis. This model posits that impaired lipid metabolism, combined with insulin resistance and metabolic imbalance, initiates inflammatory cascades, gut dysbiosis, and the accumulation of toxic metabolites, ultimately promoting fibrosis and accelerating MASLD progression to irreversible hepatocellular carcinoma (HCC). AMPK plays a multifaceted protective role against these pathological conditions by regulating several key downstream signaling pathways. It regulates biological effectors critical to metabolic and inflammatory responses, such as SIRT1, Nrf2, mTOR, and TGF-β, through complex and interrelated mechanisms. Due to these intricate connections, AMPK’s role is pivotal in managing metabolic and inflammatory disorders. In this review, we demonstrate the specific roles of AMPK and its related pathways. Several agents directly activate AMPK by binding as agonists, while some others indirectly activate AMPK by modulating upstream molecules, including adiponectin, LKB1, and the AMP: ATP ratio. As AMPK activators can target each stage of MASLD progression, the development of AMPK activators offers immense potential to expand therapeutic strategies for liver diseases such as MASH, MASLD, and liver fibrosis.

AMP-activated protein kinase (AMPK) activators have garnered significant attention for their potential to prevent the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) into liver fibrosis and to fundamentally improve liver function. The broad spectrum of pathways regulated by AMPK activators makes them promising alternatives to conventional liver replacement therapies and the limited pharmacological treatments currently available. In this study, we aim to illustrate the newly detailed multiple mechanisms of MASLD progression based on the multiple-hit hypothesis. This model posits that impaired lipid metabolism, combined with insulin resistance and metabolic imbalance, initiates inflammatory cascades, gut dysbiosis, and the accumulation of toxic metabolites, ultimately promoting fibrosis and accelerating MASLD progression to irreversible hepatocellular carcinoma (HCC). AMPK plays a multifaceted protective role against these pathological conditions by regulating several key downstream signaling pathways. It regulates biological effectors critical to metabolic and inflammatory responses, such as SIRT1, Nrf2, mTOR, and TGF-β, through complex and interrelated mechanisms. Due to these intricate connections, AMPK’s role is pivotal in managing metabolic and inflammatory disorders. In this review, we demonstrate the specific roles of AMPK and its related pathways. Several agents directly activate AMPK by binding as agonists, while some others indirectly activate AMPK by modulating upstream molecules, including adiponectin, LKB1, and the AMP: ATP ratio. As AMPK activators can target each stage of MASLD progression, the development of AMPK activators offers immense potential to expand therapeutic strategies for liver diseases such as MASH, MASLD, and liver fibrosis.

OBJECTIVE: The objective of this study was to investigate the differences in masticatory efficiency among patients with different Angle's classes of malocclusion and to assess the correlation between masticatory efficiency and the occlusal contact area. METHODS: The mixing ability index (MAI) was calculated for measuring masticatory efficiency of 61 adult patients according to Angle's classifications of malocclusion. The study included 25, 15, and 21 patients with Angle's Class I, II, and III malocclusions, respectively. Silicone interocclusal recording material was used to measure the occlusal contact area. RESULTS: Both the MAI and occlusal contact area showed the highest average values in the Class I malocclusion group, followed by the Class II and Class III malocclusion groups. No significant difference was observed in the MAI values between the Class I and Class II malocclusion groups (p > 0.05), whereas a significant difference was observed between the Class I and Class III malocclusion groups (p < 0.01) and between the Class II and Class III malocclusion groups (p < 0.05). A weak positive correlation was also observed between the MAI and occlusal contact area (p < 0.01, r² = 0.13). CONCLUSIONS: The results of this study indicated that masticatory efficiency was the highest in patients with Angle's Class I malocclusion, followed by those with Angle's Class II and Angle's Class III malocclusions. Moreover, a weak positive correlation was observed between masticatory efficiency and the occlusal contact area.
Adult ; Classification ; Humans ; Malocclusion* ; Mastication ; Silicon ; Silicones

OBJECTIVE: To assess the clinical efficacy and safety of intra-articular injection of hyaluronic acid (HA) combined with polydeoxyribonucleotide (PDRN) in patients with knee osteoarthritis in comparison with that of HA alone. METHODS: The current single-center, prospective, randomized, double-blind, controlled study was conducted in 36 patients with knee osteoarthritis at our medical institution. All the eligible patients (n=30) were equally assigned to two treatment arms (trial group ‘HA+PDRN’ and control group ‘HA’). For efficacy assessment, the patients were evaluated for the visual analogue scale (VAS) scores, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Knee Society Scores (KSS), all of which served as efficacy outcome measures. We monitored time-dependent changes in efficacy outcome measures at baseline and 1, 3 and 6 months. Subsequently, we compared differences in changes in efficacy outcome measures at 6 months from baseline between the two groups. Moreover, we assessed the safety based on the treatment-emergent adverse events (TEAEs), adverse drug reactions (ADRs) and any other complications serving as safety outcome measures. RESULTS: There were significant differences in changes in the VAS scores, the WOMAC scores in all domains, except ‘Stiffness’, the total WOMAC scores, and the KSS scores in all the domains at 6 months from baseline between the two groups (p<0.05). In our series, there were no TEAEs, ADRs, and any other complications. CONCLUSION: Intra-articular injections of HA combined with PDRN can also be considered in the treatment of knee osteoarthritis. However, further large-scale and multi-center studies are required to demonstrate the potential of the proposed combination.
Arm ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Hyaluronic Acid ; Injections, Intra-Articular ; Knee ; Ontario ; Osteoarthritis ; Osteoarthritis, Knee ; Outcome Assessment (Health Care) ; Polydeoxyribonucleotides ; Prospective Studies ; Treatment Outcome

OBJECTIVE: To assess the efficacy and safety of our 4-week caregiver-mediated exercise (CME) in improving trunk control capacity, gait, and balance and in decreasing concerns about post-stroke falls when there is an increase in its efficacy. METHODS: Acute or subacute stroke survivors were assigned to either the trial group (n=35) or the control group (n=37). Changes in Modified Barthel Index (MBI), Functional Ambulation Categories (FAC), Berg Balance Scale (BBS), and Trunk Impairment Scale (TIS) scores at 4 weeks from baseline served as primary outcome measures. Correlations of primary outcome measures with changes in Fall Efficacy Scale-International (FES-I) scores at 4 weeks from baseline in the trial group served as secondary outcome measures. Treatment-emergent adverse events (TEAEs) served as safety outcome measures. RESULTS: There were significant differences in changes in MBI, FAC, BBS, TIS-T, TIS-D, TIS-C, and FES-I scores at 4 weeks from baseline between the two groups (all p < 0.0001). There were no significant (p=0.0755) differences in changes in TIS-S scores at 4 weeks from baseline between the two groups. MBI, FAC, BBS, and TIS scores showed significantly inverse correlations with FES-I scores in patients receiving CME. There were no TEAEs in our series. CONCLUSION: CME was effective and safe in improving the degree of independence, ambulation status, dynamic and static balance, trunk function, and concerns about post-stroke falls in stroke survivors.
Accidental Falls ; Caregivers ; Gait ; Humans ; Outcome Assessment (Health Care) ; Postural Balance ; Rehabilitation* ; Stroke ; Survivors ; Walking

OBJECTIVE: Epidural hematoma of posterior fossa is less common than epidural hematoma of supratentorial area, and there are not many articles about epidural hematoma of posterior fossa. This study investigated patients who underwent surgery of epidural hematoma of posterior fossa, and the relation between the clinical manifestation and postoperative outcome. METHODS: A retrospective analysis performed of 27 patients who underwent operation for acute traumatic epidural hematoma of posterior fossa from January 2004 to December 2011. Analyzed factors were gender, age, Glasgow Coma Scale (GCS) measured upon presentation to the hospital, preoperative GCS score, cause of trauma, time elapsed from the accident to the presentation to the hospital, time elapsed from the presentation to the hospital to the surgery, radiographic findings (brain CT findings), and Glasgow Outcome Scale (GOS). RESULTS: Two patients (7.4%) had GCS score on admission of 3-8, 11 (29.6%) had 9-12, and 17 (66.7%) had 13-15. In 1 (3.7%) patient, GCS score changed from 13 to 10, and preoperative GCS score was significantly correlated with GOS score (p<0.05). Mean thickness of hematoma was 19.3+/-7.5 mm, and was significantly correlated with GOS score (p<0.05). GOS score was 4-5 in 24 patients (88.9%), 3 (severe disability) in 1 patient (3.7%), and 1 (death) in 2 patients (7.4%). CONCLUSION: In the patients underwent surgery for epidural hematoma of posterior fossa, 88.9% had favorable outcome (in GOS score of 4 or more). Preoperative GCS score and thickness of hematoma on brain computed tomography are important determinants of prognosis.
Brain ; Cranial Fossa, Posterior ; Glasgow Coma Scale ; Glasgow Outcome Scale ; Hematoma ; Humans ; Prognosis ; Retrospective Studies

OBJECTIVE: Spontaneous cerebellar hemorrhage (SCH) is less common than supratentorial intracerebral hemorrhage. This study investigated the treatment of SCH and the relation between its clinical and radiological manifestation and outcome. MATERIALS AND METHODS: We presented a SCH management protocol in our institute and analyzed the clinical and radiological findings in 41 SCH patients. The outcomes of each method (surgery and conservative treatment) were compared among patients with initial Glasgow Coma Scale (GCS) score of 9-13 and hematoma volume greater than 10 mL. RESULTS: Two (4.9%), 16 (39%), and 23 (56.1%) patients had an initial GCS score of 3-8, with 3-8, 9-13, and 14-15, respectively. Initial GCS score showed significant correlation with Glasgow Outcome Scale (GOS) score (p = 0.005). The mean largest hematoma diameter was 3.2 +/- 1.5 cm, and the mean volume was 11.0 +/- 11.5 mL. Both of them showed significant inverse correlation with GOS score (p < 0.001). Among patients with an initial GCS score of 9-13 and hematoma volumes greater than 10 mL, 3 (50%) had good outcome and 3 (50%) had poor outcome in the surgical, and all of those in the conservative treatment group had poor outcomes. The outcome distribution differed significantly in the surgical and conservative groups (p = 0.030). CONCLUSION: Initial GCS score and largest hematoma diameter and volume on brain computed tomography are important determinants of outcome in SCH patients. The surgery group showed better outcome than the conservative treatment group among those with an intermediate neurological status and large hematomas.
Brain ; Cerebellum ; Cerebral Hemorrhage ; Glasgow Coma Scale ; Glasgow Outcome Scale ; Hematoma ; Hemorrhage* ; Humans

OBJECTIVE: Spontaneous cerebellar hemorrhage (SCH) is less common than supratentorial intracerebral hemorrhage. This study investigated the treatment of SCH and the relation between its clinical and radiological manifestation and outcome. MATERIALS AND METHODS: We presented a SCH management protocol in our institute and analyzed the clinical and radiological findings in 41 SCH patients. The outcomes of each method (surgery and conservative treatment) were compared among patients with initial Glasgow Coma Scale (GCS) score of 9-13 and hematoma volume greater than 10 mL. RESULTS: Two (4.9%), 16 (39%), and 23 (56.1%) patients had an initial GCS score of 3-8, with 3-8, 9-13, and 14-15, respectively. Initial GCS score showed significant correlation with Glasgow Outcome Scale (GOS) score (p = 0.005). The mean largest hematoma diameter was 3.2 +/- 1.5 cm, and the mean volume was 11.0 +/- 11.5 mL. Both of them showed significant inverse correlation with GOS score (p < 0.001). Among patients with an initial GCS score of 9-13 and hematoma volumes greater than 10 mL, 3 (50%) had good outcome and 3 (50%) had poor outcome in the surgical, and all of those in the conservative treatment group had poor outcomes. The outcome distribution differed significantly in the surgical and conservative groups (p = 0.030). CONCLUSION: Initial GCS score and largest hematoma diameter and volume on brain computed tomography are important determinants of outcome in SCH patients. The surgery group showed better outcome than the conservative treatment group among those with an intermediate neurological status and large hematomas.
Brain ; Cerebellum ; Cerebral Hemorrhage ; Glasgow Coma Scale ; Glasgow Outcome Scale ; Hematoma ; Hemorrhage* ; Humans