Depletion of Numb and Numblike in Murine Lung Epithelial Cells Ameliorates Bleomycin-Induced Lung Fibrosis by Inhibiting the β-Catenin Signaling Pathway

Idiopathic pulmonary fibrosis (IPF) represents the most aggressive form of pulmonary fibrosis (PF) and is a highly debilitating disorder with a poorly understood etiology. The lung epithelium seems to play a critical role in the initiation and progression of the disease. A repeated injury of lung epithelial cells prompts type II alveolar cells to secrete pro-fibrotic cytokines, which induces differentiation of resident mesenchymal stem cells into myofibroblasts, thus promoting aberrant deposition of extracellular matrix (ECM) and formation of fibrotic lesions. Reactivation of developmental pathways such as the Wnt-β-catenin signaling cascade in lung epithelial cells plays a critical role in this process, but the underlying mechanisms are still enigmatic. Here, we demonstrate that the membrane-associated protein NUMB is required for pathological activation of β-catenin signaling in lung epithelial cells following bleomycin-induced injury. Importantly, depletion of Numb and Numblike reduces accumulation of fibrotic lesions, preserves lung functions, and increases survival rates after bleomycin treatment of mice. Mechanistically, we demonstrate that NUMB interacts with casein kinase 2 (CK2) and relies on CK2 to activate β-catenin signaling. We propose that pharmacological inhibition of NUMB signaling may represent an effective strategy for the development of novel therapeutic approaches against PF.

Agnikarma (therapeutic heat burn) an unique approach in the management of vatakantaka w.s.r. to plantar fasciitis- A single Case Report

Heel pain is most common condition now days and the ratio of occurrence observed is 1 out of 10 people suffered once during their life period. There are so many conditions causing heel pain among that Plantar fasciitis is one which is having high prevalence rate. In Ayurveda Plantar fasciitis can be corelated with Vatakantaka. Walking on uneven surface and repeated injury leads to Vata prakopa due to that it develops pricking type of pain like thorn in heel region and ultimately leads to Vatakantaka. This is the small evidence to support traditional treatment modalities to describe for management of Vatakantaka (planter fasciitis). A 47year old male patient complaining of pain in right heel region for 5 months along with difficulty in walking after awakening from bed at morning. Then patient was treated in outdoor patient department with 4 successive sittings of bindu dagdha Agnikarma at posterior medial side of right heel region in 7 days interval along with Rasna Saptaka Kwatha 20 ml empty stomach orally two times a day for 1 month. After 1 month of treatment, patient got complete relief in pain and stiffness.

REPEATED INJURY PROMOTES TRACHEOBRONCHIAL TISSUE STEM CELL ATTRITION

Chronic lung disease has been attributed to stem cell aging and/or exhaustion. To address this issue, we investigated the lifespan of tracheobronchial tissue stem cells (TSC) over time and in response to repeated injury. Chromatin and nucleotide labeling studies in mice indicated that: 1) injury activated a subset of the TSC pool and that this process conserved TSC over time; and 2) activated TSC were predisposed to further proliferation and this activated state lead to terminal differentiation. Analysis of human TSC and clonal isolates indicated that repeated TSC proliferation led to telomere shortening and analysis of TSC from Dyskeratosis Congenita donors indicated that mutations in telomere biology genes accelerated TSC depletion. RNAseq and functional studies indicated that human TSC terminated as a secretory committed cell. These data support a model in which a repeated epithelial injury depletes the TSC pool and initiates the abnormal repair associated with chronic lung disease.

Vatakantaka and its management through Ayurveda- A Case review.

Vatakantaka is characterized by pain in the heel region and included in Vatavyadhi by Acharya Sushruta. It causes due to silent and repeated injury resulting into inflammation of plantar fascia which results in the painful heel. It is a common cause of heel pain occurs in about 10% of the general population. Women are twice more prevalent than men. Vatakantaka is mainly caused due to vitiation of Vatadosha and continuous pressure on the heel region. It can be correlated with Chronic planter fasciitis or Calcaneal spur. It is more prevalent in female gender and having Sthul akruti (obesity). Various chikitsa measures for management of Vatakantaka are given in classics of Ayurveda. Here bahya and abhyantar chikitsa with Agnikarma gives improvement in subjective criteria like vedana (pain), stambha (stiffness), shotha (swelling) and kriyahani (restricted movements) in short duration of time.

Altered corticomotor latencies but normal motor neuroplasticity in concussed athletes

We are the first to assess corticomotor latencies and motor neuroplasticity in a common group of collegiate athletes across different phases of injury and recovery. We found that the number of concussions an individual sustains negatively impacts corticomotor latencies with a higher number of prior concussions correlating positively with longer latencies. Our findings indicate that concussions may lead to permanent changes in the corticospinal tract that are exacerbated by repeated injury.

The Role of Agni karma in the management of Planter Fasciitis

Planter fasciitis is commonly found in 80% population in the society which is caused due to the affection of calcaneum. It is often seen in females and individuals over 35 years. It is one of the most troublesome complaints affecting the individuals in their routine work. Acharya Sushruta suggests the disease planter fasciitis can be correlated with Vatakantaka which is caused by vitiated Vata dosha due to constant standing and walking. Planter fasciitis can develop due to walking on uneven roads with ill fitting footwear which causes silent and repeated injury resulting into inflammation of planter fascia which results into painful heel, tenderness, early morning stiffness & restricted movements of heel. Sushruta has mentioned different methods of management of diseases, such as Bheshaja karma, Kshara karma, Agni karma, Shastrakarma and Raktamokshana. Aim-To study the role of Agnikarma in the management of Planter Fascitis. Objectives: To study planter fasciitis.To study the role of Agnikarma in planter fasciitis. Results and Discussion: Chronic Planter fasciitis can develop due to use of walking on uneven roads with ill fitting footwear which causes silent and repeates injury resulting into inflammation of planter fascia which results into painful heel, tenderness, restricted movements of heel, During the use of Agnikarma chikitsa, we take the Agni in the shalaka by making it Red Hot on fire. The Agni from shalaka is to be transferred to the diseased part, the dhatoo (twacha). The Dhatu Agni gets utkleshit (Activated). The activated dhatoo Agni use to produce Dosh Pachan.

Concussion and sports-related head injury

Interest in concussion and sports-related injury has intensified in recent years for three main reasons: (1) it is a preventable form of brain injury; (2) there is increasing evidence that repeated injury can result in long-term neurocognitive loss; and (3) as a result there are potential medicolegal costs to organizations that, possibly inadvertently, allow this form of brain injury to occur within their sport. The long-term effects of boxing resulting in dementia pugilistica have been appreciated for some time, however the results of repeated mild head injury in other sports is now under focus. Concussion, increasingly termed mild traumatic brain injury, should be graded. Imaging, removal from, and return to sport are all discussed in this chapter.